CSC-3436 sensitizes triple negative breast cancer cells to TRAIL-induced apoptosis through ROS-mediated p38/CHOP/death receptor 5 signaling pathways.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) shows little or no toxicity in most normal cells and preferentially induces apoptosis in a variety of malignant cells. However, patients develop resistance to TRAIL, therefore, sensitizing agents that can sensitize the tumor cells to TRAIL-mediated apoptosis are necessary. In this study, we investigated the effect of 2-(3-hydroxyphenyl)-5-methylnaphthyridin-4-one (CSC-3436), an useful flavonoid, to overcome the TRAIL-resistant triple negative breast cancer (TNBC) cells. We found that CSC-3436 potentiated TRAIL-induced apoptosis in TRAIL-resistant TNBC cells and this correlated with the upregulation of death receptors (DR)-5 and down-regulation of decreased decoy receptor (DcR)-1 expression. When examined for its mechanism, we found that the decreased expression of anti-apoptotic proteins c-FLIPS/L, Bcl-Xl, Bcl-2, Survivin, and XIAP. CSC-3436 would increase the expression of Bax and promoted the cleavage of bid. In addition, the induction of DR5 by CSC-3436 was found to be dependent on the modulation of reactive oxygen species (ROS)/p38/C/EBP-homologous protein (CHOP) signaling pathways. Overall, our results indicated that CSC-3436 could potentiate the apoptotic effects of TRAIL through down-regulation of cell survival proteins and upregulation of DR5 via the ROS-mediated upregulation of CHOP protein.

Demethoxycurcumin induces apoptosis in HER2 overexpressing bladder cancer cells through degradation of HER2 and inhibiting the PI3K/Akt pathway.

Bladder cancer is the most common malignancy of the urinary tract and arising from the epithelial lining of the urinary bladder. Resistance to cytotoxic therapies is associated with overexpression of oncogenic proteins; including HER2, and Akt in chemotherapy resistance of bladder cancer. Various studies demonstrated that curcuminoids, the most important active phenolic compounds of turmeric (Curcuma longa), have anti-tumor activities in a wide range of human malignant cell lines. The aim of this study is to evaluate whether curcuminoids (curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin) could repress the expression of HER2 in HER2-overexpressing bladder cancer cells. Among the test compounds, DMC significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing bladder cancer cells. DMC decreases HER2 level through inhibiting the interaction of HER2 and Hsp90. Our study also indicated that DMC showed additive activity in combination with chemotherapeutic agents, including paclitaxel and cisplatin. These findings show that DMC should be developed further as a new antitumor drug candidate for treatment of HER2-overexpressing bladder cancer.

Restoration of HDAC1 Enzymatic Activity after Stroke Protects Neurons from Ischemia/Reperfusion Damage and Attenuates Behavioral Deficits in Rats.

A therapeutic approach for promoting neuroprotection and brain functional regeneration after strokes is still lacking. Histone deacetylase 1 (HDAC1), which belongs to the histone deacetylase family, is involved in the transcriptional repression of cell-cycle-modulated genes and DNA damage repair during neurodegeneration. Our previous data showed that the protein level and enzymatic activity of HDAC1 are deregulated in stroke pathogenesis. A novel compound named 5104434 exhibits efficacy to selectively activate HDAC1 enzymatic function in neurodegeneration, but its potential in stroke therapy is still unknown. In this study, we adopted an induced rat model with cerebral ischemia using the vessel dilator endothelin-1 to evaluate the potential of compound 5104434. Our results indicated compound 5104434 selectively restored HDAC1 enzymatic activity after oxygen and glucose deprivation, preserved neurite morphology, and protected neurons from ischemic damage in vitro. In addition, compound 5104434 attenuated the infarct volume, neuronal loss, apoptosis, DNA damage, and DNA breaks in cerebral ischemia rats. It further ameliorated the behavioral outcomes of neuromuscular response, balance, forepaw strength, and functional recovery. Collectively, our data support the efficacy of compound 5104434 in stroke therapy and contend that it can be considered for clinical trial evaluation.

Smoking Paradox in Stroke Survivors?: Uncovering the Truth by Interpreting 2 Sets of Data.

Background and Purpose- The observation that smokers with stroke could have better outcome than nonsmokers led to the term "smoking paradox." The controversy of such a complex claim has not been fully settled, even though different case mix was noted. Analyses were conducted on 2 independent data sets to evaluate and determine whether such a paradox truly exists. Methods- Taiwan Stroke Registry with 88 925 stroke cases, and MJ cohort with 541 047 adults participating in a medical screening program with 1630 stroke deaths developed during 15 years of follow-up (1994-2008). Primary outcome for stroke registry was functional independence at 3 months by modified Rankin Scale score ≤2, for individuals classified by National Institutes of Health Stroke Scale score at admission. For MJ cohort, mortality risk by smoking status or by stroke history was assessed by hazard ratio. Results- A >11-year age difference in stroke incidence was found between smokers and nonsmokers, with a median age of 60.2 years for current smokers and 71.6 years for nonsmokers. For smokers, favorable outcome in mortality and in functional assessment in 3 months with modified Rankin Scale score ≤2 stratified by the National Institutes of Health Stroke Scale score was present but disappeared when age and sex were matched. Smokers without stroke history had a ≈2-fold increase in stroke deaths (2.05 for ischemic stroke and 1.53 for hemorrhagic stroke) but smokers with stroke history, 7.83-fold increase, overshadowing smoking risk. Quitting smoking at earlier age reversed or improved outcome. Conclusions- "The more you smoke, the earlier you stroke, and the longer sufferings you have to cope." Smokers had 2-fold mortality from stroke but endured stroke disability 11 years longer. Quitting early reduced or reversed the harms.

Is traumatic brain injury a risk factor for neurodegeneration? A meta-analysis of population-based studies.

BACKGROUND: To determine the association of prior traumatic brain injury (TBI) with subsequent diagnosis of neurodegeneration disease. METHODS: All studies from 1980 to 2016 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, Embase, study references, and review articles. The data and study design were assessed by 2 investigators independently. A meta-analysis was performed by RevMan 5.3. RESULTS: There were 18 studies comprising 3,263,207 patients. Meta-analysis revealed a significant association of prior TBI with subsequent dementia. The pooled odds ratio (OR) for TBI on development of dementia, FTD and TDP-43 associated disease were 1.93 (95% CI 1.47-2.55, p < 0.001), 4.44 (95% CI 3.86-5.10, p < 0.001), and 2.97 (95% CI 1.35-6.53, p < 0.001). However, analyses of individual diagnoses found no evidence that the risk of Alzheimer's disease, and Parkinson's disease in individuals with previous TBI compared to those without TBI. CONCLUSIONS: History of TBI is not associated with the development of subsequent neurodegeneration disease. Care must be taken in extrapolating from these results because no suitable criteria define post TBI neurodegenerative processes. Therefore, further research in this area is needed to confirm these questions and uncover the link between TBI and neurodegeneration disease.

The risk of cataractogenesis after gamma knife radiosurgery: a nationwide population based case-control study.

BACKGROUND: Medical radiation is considered a factor responsible for cataractogenesis. However, the incidence of this ophthalmologic complication resulting from gamma knife radiosurgery (GKRS) has not yet been reported. The present study aimed to determine the risk of cataractogenesis associated with radiation exposure from GKRS. METHODS: This study used information from a random sample of one million persons enrolled in the nationally representative Taiwan National Health Insurance Research Database. The GK group consisted of patients who underwent GKRS between 2000 and 2009. The non-GK group was composed of subjects who had never undergone GKRS, but who were matched with the case group for time of enrollment, age, sex, history of coronary artery disease, hypertension, and diabetes. RESULTS: There were 277 patients in the GK group and 2770 matched subjects in the non-GK group. The GK group had a higher overall incidence of cataracts (10.11% vs. 7.26%; crude hazard ratio [cHR], 1.59; 95% CI, 1.07-2.36; adjusted hazard ratio [aHR], 1.25; 95% CI, 0.82-1.90) than the non-GK group. Patients who had undergone computed tomography and/or cerebral angiography (CT/angio) studies had a higher risk of developing cataracts than those who did not (10.82% vs. 6.64%; cHR, 1.74; 95% CI, 1.31-2.30; aHR, 1.65; 95% CI, 1.22-2.23). The age group between 30 and 50 years had the highest risk of cataractogenesis in both the GK and CT/angio groups (cHR, 3.50; 95% CI, 1.58-7.72; aHR, 2.43; 95% CI, 1.02-5.81; cHR, 2.96; 95% CI, 1.47-5.99; aHR, 2.27; 95% CI, 1.05-4.93, respectively). CONCLUSIONS: Radiation exposure due to GKRS and CT/angio study may be independently associated with increased risk of cataractogenesis. We suggest routine dosimetry measurement of eye lens and proper protection for patients with benign lesions during GKRS. Regular follow-up imaging studies should avoid the use of CT/angio, and particular care should be taken in the 30-50-year-old age group, due to their significantly increased risk of cataract formation.

The GLP-1 receptor agonists exendin-4 and liraglutide alleviate oxidative stress and cognitive and micturition deficits induced by middle cerebral artery occlusion in diabetic mice.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) analogs protect a variety of cell types against oxidative damage and vascular and neuronal injury via binding to GLP-1 receptors. This study aimed to investigate the effects of the GLP-1 analogs exendin-4 and liraglutide on cerebral blood flow, reactive oxygen species production, expression of oxidative stress-related proteins, cognition, and pelvic sympathetic nerve-mediated bladder contraction after middle cerebral artery occlusion (MCAO) injury in the db/db mouse model of diabetes. RESULTS: Sixty minutes of MCAO increased blood and brain reactive oxygen species counts in male db/db mice, as revealed by dihydroethidium staining. MCAO also increased nuclear factor-κB and intercellular adhesion molecule-1 expression and decreased cerebral microcirculation. These effects were attenuated by treatment with exendin-4 or liraglutide. MCAO did not affect basal levels of phosphorylated Akt (p-Akt) or endothelial nitric oxide synthase (p-eNOS); however, exendin-4 and liraglutide treatments significantly enhanced p-Akt and p-eNOS levels, indicating activation of the p-Akt/p-eNOS signaling pathway. MCAO-induced motor and cognitive deficits and micturition dysfunction, indicated by reduced pelvic nerve-mediated voiding contractions and increased nonvoiding contractions, were also partially attenuated by exendin-4 treatment. CONCLUSIONS: The above data indicate that treatment with GLP-1 agonists exerts protective effects against oxidative, inflammatory, and apoptotic damage in brain areas that control parasympathetic/pelvic nerve-mediated voiding contractions and cognitive and motor behaviors in a diabetic mouse model.

Mood disorders after traumatic brain injury in adolescents and young adults: a nationwide population-based cohort study.

OBJECTIVE: To delineate the relationship between traumatic brain injury (TBI) and mood disorders from population-based data in Taiwan. STUDY DESIGN: This prospectively followed cohort study involved a subset of the National Health Insurance Research Database containing complete inpatient and outpatient data of 1 million randomly drawn beneficiaries. We included 10- to 24-year-old patients (n = 15,203) receiving the diagnosis of TBI in ambulatory visits or hospitalization from 2000-2004 and their age- and sex-matched comparison insureds using health service in the same year (n = 76,015). Diagnosis of mood disorders was recorded within 5 years after the traumatic event or index use of health service. Baseline demographics, clinical characteristics, and premorbid psychiatric conditions were compared using χ(2) analysis. Increased risk during the 5-year follow-up period was represented by crude and adjusted hazard ratios with 95% CI using a Cox proportional hazard regression. RESULTS: A total of 451/15,203 patients with TBI (2.97%) received a diagnosis of mood disorders in the 5-year follow-up period compared with 1153/97,445 individuals (1.52%) without antecedent TBI. After adjusting for select premorbid comorbidities, TBI remained a significant predisposing factor with a 1.96-fold (95% CI 1.74-2.22) increase in risk of mood disorders. CONCLUSIONS: Our findings show a higher likelihood of manifesting mood disorders in adolescents and young adults who sustained a prior TBI. Health professionals should carefully monitor both the physical and psychological impacts of head trauma.

Increased risk of hip fractures in patients with dementia: a nationwide population-based study.

BACKGROUND: Dementia has been associated with an increased risk of hip fracture. However, little research has been conducted on the impact of dementia on wrist or vertebral fracture development. The aim of this study was to investigate whether dementia is a risk factor for different types of fracture in Taiwan. METHODS: The study sample was drawn from Taiwan's National Health Insurance Research Database of reimbursement claims, and comprised 1408 patients who visited ambulatory care centers or were hospitalized with a diagnosis of dementia. The comparison group consisted of 7040 randomly selected individuals. Cox proportional hazard regression model was used to examine associations between dementia and the risk of different types of fracture. RESULTS: During a 3-year follow-up period, 264 patients with dementia (18.75%) and 1098 patients without dementia (15.60%) developed fractures. Dementia was independently associated with increased risk of hip fracture [adjusted hazard ratio (HR) 1.92, 95% CI 1.48-2.49]. Patients with dementia and osteoporosis had the highest risk of developing hip fracture (adjusted HR 2.27, 95% CI 1.28-4.01). Dementia did not increase wrist fracture or vertebral fracture risk when compared to the control group, even in patients with osteoporosis. CONCLUSIONS: Individuals with dementia are at greater risk of developing hip fracture, particularly if they also have osteoporosis. Early mental screening programs and health education should be initiated to decrease disability and dependence in patients with dementia.

Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells.

BACKGROUND: Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored. METHODS: To investigate the parameters impacting EMT during PD therapy, 53 clinical stable PD patients were enrolled. EMT assessments were conducted through human peritoneal MCs cultured from dialysate effluent with one consistent standard criterion (MC morphology and the expression of an epithelial marker, cytokeratin 18). The factors potentially associated with EMT were analyzed using logistic regression analysis. Primary MCs derived from the omentum were isolated for the in vitro study. RESULTS: Forty-seven percent of the patients presented with EMT, 28% with non-EMT, and 15% with a mixed presentation. Logistic regression analysis showed that patients who received persistent PD therapy (dwelling time of 24 h/day) had significantly higher EMT tendency. These results were consistent in vitro. CONCLUSIONS: Dwelling time had a significant effect on the occurrence of EMT on MCs.

Systematic Review and Meta-analysis of Radial or Femoral Access for Carotid Stenting.

PURPOSE: There is a growing interest in performing coronary artery and neurovascular interventions via the radial artery; however, few studies have examined the outcomes of transradial carotid stenting. Therefore, our study aimed to compare cerebrovascular outcomes and crossover rates in carotid stenting between transradial and traditional transfemoral approaches. METHODS: A systematic review was performed by searching three electronic databases from inception to June 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In addition, random effect meta-analysis was used to pool the odds ratios (ORs) for stroke, transient ischemic attack, major adverse cardiac events, death, major vascular access site complications, and procedure crossover rates between the transradial and transfemoral approaches. RESULTS: A total of 6 studies were included involving a total of n = 567 transradial and n = 6176 transfemoral procedures. The ORs for stroke, transient ischemic attack, and major adverse cardiac events were 1.43 (95% confidence interval, CI 0.72-2.86, I2 = 0), 0.51 (95% CI 0.17-1.54, I2 = 0), and 1.08 (95% CI 0.62-1.86, I2 = 0), respectively. Neither the major vascular access site complication rate (OR 1.11, 95% CI 0.32-3.87, I2 = 0) nor crossover rate (OR 3.94, 95% CI 0.62-25.11, I2 = 57%) showed statistically significant differences between the two approaches. CONCLUSION: The modest quality of the data suggested comparable procedural outcomes between the transradial and transfemoral approaches when performing carotid stenting; however, high level evidence regarding postoperative brain images and risk of stroke in transradial carotid stenting are lacking. Therefore, it is reasonable for interventionists to weigh up the risks of neurological events and potential benefits, including fewer access site complications, before choosing the radial or femoral arteries as access sites. Future large-scale randomized controlled trials are imperative.

Simple coiling of middle meningeal artery embolization for chronic subdural hematoma: An inverse probability of treatment weighting matched cohort study.

BACKGROUND: Middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) has gained much attention in recent years. However, unintended embolization may occur when employing liquid embolic agents or particles. We present our clinical experience in simple coiling of MMAE to manage CSDH. METHODS: Patients underwent either surgical evacuation or MMAE with simple coiling for CSDH were reviewed. Clinical and radiographic outcomes were assessed at admission, 1-month, and 6-month intervals. Two treatment groups were matched with inverse probability of treatment weighting. RESULTS: One hundred twelve patients were included, with 27 patients in MMAE group and 87 patients in surgery group. In MMAE group, significant reductions were observed in hematoma width (admission vs. 1-month, 2.04 [1.44-2.60] cm vs. 0.62 [0.37-0.95] cm, p < 0.001). The adjusted odds ratio (aOR) of surgical rescue rate (0.77 95%CI 0.13-4.47, p = 0.77), hematoma reduction (>50%) (0.21 95%CI 0.04-1.07, p = 0.06), and midline shift improvement rate (3.22, 95%CI 0.84-12.4, p = 0.09) had no substantial disparities between two groups at 1-month follow-up. In addition, no significant difference was noted between two groups in terms of hematoma reduction (>50%) at 6-month follow-up (aOR 1.09 95%CI 0.32-3.70, p = 0.89). No procedure-related complications were found in MMA embolization group. CONCLUSION: Simple coiling for MMA had comparable outcomes with surgical evacuation for CSDH. Our findings suggest that simple coiling can be an alternative choice for liquid agents or particles in MMA embolization for CSDH with acceptable safety.

Tranexamic acid versus placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial.

BACKGROUND: Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo. METHODS: STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete. FINDINGS: Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98]). INTERPRETATION: Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings. FUNDING: Australian Government Medical Research Future Fund.

A comparison of the Trachway intubating stylet and the Macintosh laryngoscope in tracheal intubation: a manikin study.

PURPOSE: The Trachway intubating stylet (Trachway(®)), when used by experienced anesthesiologists, has been shown to be effective for difficult airway management. We evaluated the efficacy of this intubating stylet for tracheal intubation in a manikin when used by experienced laryngoscopists with little experience using this device. METHODS: Thirty-eight nurse anesthesiologists intubated the trachea of a manikin (Laerdal Airway Management Trainer) with a Trachway intubating stylet or a Macintosh laryngoscope in easy and difficult laryngoscopy scenarios. The duration of the intubation attempts, success rates, dental trauma, and ease of use (0 = very easy; 10 = very difficult) were recorded. The primary endpoint was the duration of the successful tracheal intubation attempt in the difficult laryngoscopy scenario. Data are presented as means (SD). RESULTS: Both devices resulted in similar tracheal intubation performance in the easy laryngoscopy scenario. However, the Trachway intubating stylet provided shorter intubation times (20.8 ± 5.6 vs. 25.5 ± 7.3 s; p = 0.003) and easier intubations (2.4 ± 1.6 vs. 5.7 ± 1.8; p < 0.001) compared with the Macintosh laryngoscope in the difficult laryngoscopy scenario. All tracheal intubations were successful and no dental trauma was observed when using the Trachway intubating stylet. CONCLUSION: We concluded that the Trachway intubating stylet, when used by novices, is effective in both easy and difficult laryngoscopy scenarios. In difficult laryngoscopy scenarios, this device provided faster, easier, and less traumatic intubation than the Macintosh laryngoscope.

Endovascular treatment in bilateral cavernous sinus dural arteriovenous fistulas: a systematic review and meta-analysis.

Few studies have discussed the disease nature and treatment outcomes for bilateral cavernous sinus dural arteriovenous fistula (CSDAVF). This study aimed to investigate the clinical features and treatment outcomes of bilateral CSDAVF. Embase, Medline, and Cochrane library were searched for studies that specified the outcomes of bilateral CSDAVF from inception to April 2022. The classification, clinical presentation, angiographic feature, surgical approach, and treatment outcomes were collected. Meta-analysis was performed using the random effects model. Eight studies reporting 97 patients were included. The clinical presentation was mainly orbital (n = 80), cavernous (n = 52) and cerebral (n = 5) symptoms. The most approached surgical route was inferior petrosal sinus (n = 80), followed by superior orbital vein (n = 10), and alternative approach (n = 7). Clinical symptoms of 88% of the patients (95% CI 80-93%, I2 = 0%) were cured, and 82% (95% CI 70-90%, I2 = 7%) had angiographic complete obliteration of fistulas during follow up. The overall complication rate was 18% (95% CI 11-27%, I2 = 0%). Therefore, endovascular treatment is an effective treatment for bilateral CSDAVF regarding clinical or angiographic outcomes. However, detailed evaluation of preoperative images and comprehensive surgical planning of the approach route are mandatory owing to complexity of the lesions.

Quantitative Analysis of Brain Swelling Resolution With Regard to Cranioplasty After Decompressive Craniectomy.

OBJECTIVE: Adequate brain swelling resolution prior to cranioplasty (CP) is an important yet loosely defined issue. Despite efforts to balance timely CP and patient safety, heterogeneous study methodologies have led to conflicting results. This study aims to standardize this issue through quantifying degree of brain swelling resolution using a proposed Visual CP Scale. METHODS: The proposed Visual CP Scale is validated through a 2-pronged approach. The first prong involves a national survey in Taiwan, where neurosurgeons were surveyed to determine what constitutes a patient's readiness for CP. The second prong involves a large retrospective cohort, where the correlations between timing, degree of brain swelling resolution, and post-CP complication rates, are evaluated. RESULTS: In the national Taiwan CP Survey, 124 out of 772 neurosurgeons (17.2%) completed the survey. Respondents who chose higher grades on the Visual CP Scale preferred later CP timings. In the retrospective data, 378 out of 770 (49.1%) patients had pre-CP brain images, allowing for the utilization of the Visual CP Scale. A Visual CP Scale score of greater than or equal to 4 was associated with fewer complications after CP. CONCLUSIONS: The timing of CP should be determined by the degree of brain swelling resolution, not vice versa. The proposed Visual CP Scale offers an objective method for assessing brain swelling resolution, making it an adjuvant tool for clinical decision-making and future research related to CP.

HDAC1 is Involved in Neuroinflammation and Blood-Brain Barrier Damage in Stroke Pathogenesis.

Background: Stroke is a common cause of disability and mortality worldwide; however, effective therapy remains limited. In stroke pathogenesis, ischemia/reperfusion injury triggers gliosis and neuroinflammation that further activates matrix metalloproteinases (MMPs), thereby damaging the blood-brain barrier (BBB). Increased BBB permeability promotes macrophage infiltration and brain edema, thereby worsening behavioral outcomes and prognosis. Histone deacetylase 1 (HDAC1) is a repressor of epigenomic gene transcription and participates in DNA damage and cell cycle regulation. Although HDAC1 is deregulated after stroke and is involved in neuronal loss and DNA repair, its role in neuroinflammation and BBB damage remains unknown. Methods: The rats with cerebral ischemia were evaluated in behavioral outcomes, levels of inflammation in gliosis and cytokines, and BBB damage by using an endothelin-1-induced rat model with cerebral ischemia/reperfusion injury. Results: The results revealed that HDAC1 dysfunction could promote BBB damage through the destruction of tight junction proteins, such as ZO-1 and occludin, after stroke in rats. HDAC1 inhibition also increased the levels of astrocyte and microglial gliosis, tumor necrosis factor-alpha, interleukin-1 beta, lactate dehydrogenase, and reactive oxygen species, further triggering MMP-2 and MMP-9 activity. Moreover, modified neurological severity scores for the cylinder test revealed that HDAC1 inhibition deteriorated behavioral outcomes in rats with cerebral ischemia. Discussion: HDAC1 plays a crucial role in ischemia/reperfusion-induced neuroinflammation and BBB damage, thus indicating its potential as a therapeutic target.

All-Cause Standardized Mortality Ratio in Hemodialysis and Peritoneal Dialysis Patients: A Nationwide Population-Based Cohort Study.

Patients with end-stage renal disease (ESRD) are at a higher mortality risk compared with the general population. Previous studies have described a relationship between mortality and patients with ESRD, but the data on standardized mortality ratio (SMR) corresponding to different causes of death in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) are limited. This study was designed as a nationwide population-based retrospective cohort study. Incident dialysis patients between January 2000 and December 2015 in Taiwan were included. Using data acquired from the Taiwan Death Registry, SMR values were calculated and compared with the overall survival. The results showed there were a total of 128,966 patients enrolled, including 117,376 incident HD patients and 11,590 incident PD patients. It was found that 75,297 patients (58.4%) died during the period of 2000-2017. The overall SMR was 5.21. The neoplasms SMR was 2.11; the endocrine, nutritional, metabolic, and immunity disorders SMR was 13.53; the circulatory system SMR was 4.31; the respiratory system SMR was 2.59; the digestive system SMR was 6.1; and the genitourinary system SMR was 27.22. Therefore, more attention should be paid to these diseases in clinical care.

Population based study on patients with traumatic brain injury suggests increased risk of dementia.

OBJECTIVE: The relationship between traumatic brain injury (TBI) and the risk of dementia remains controversial. This population based study was designed to estimate and compare the risk of dementia in TBI and non-TBI individuals during the 5 year period after TBI. METHODS: This study was a retrospective cohort study. Data were obtained from the Longitudinal Health Insurance Database 2000. We included 44,925 patients receiving ambulatory or hospital care and 224,625 non-TBI patients; patients were matched for sex, age and year of index use of healthcare. Patients <15 years of age and those admitted to the intensive care unit were excluded. Each individual was studied for 5 years to identify the subsequent development of dementia. Data were analysed by Cox proportional hazard regression. RESULTS: During the 5 year follow-up period, 1196 TBI (2.66%) and 224,625 non-TBI patients (1.53%) patients developed dementia. During the 5 year follow-up period, TBI was independently associated with a 1.68 (range 1.57-1.80) times greater risk of dementia after adjusting for sociodemographic characteristics and selected comorbidities. CONCLUSIONS: The findings of this study suggest an increased risk of dementia among individuals with TBI. We suggest the need for more intensive medical monitoring and health education in individuals with TBI.

Treatment, Outcome, and Relapse of Spontaneous and Nonspontaneous Cerebrospinal Fluid Leak.

Cerebrospinal fluid (CSF) leak can be spontaneous or nonspontaneous. The management options include conservative treatments, blood patch, and surgical repairs. We compared clinical symptoms, image findings, management options, hospitalization, and relapse rates among different causes of CSF leaks. Eighty-one patients were recruited: 20 with spontaneous and 61 with nonspontaneous CSF leaks. Nonspontaneous causes included lumbar puncture, surgery, and trauma. Surgery sites comprised sphenoid, spine, skull base, and calvaria. Spontaneous CSF leak came from the sphenoid or spine. Age, gender, body mass index, initial symptoms, hospitalization, treatment courses, and recurrence rates showed no difference between the groups. The spontaneous group had higher CSF accumulations on their MRIs. MRI pachymeninge enhancement showed the highest sensitivity (78.6%) for intracranial hypotension. Meningitis occurred in 1/3 of sphenoid, skull base, and calvarian surgeries. Earlier reoperation was correlated with shorter hospitalization (r = 0.651), but the recurrence rates were similar. Longer intervals between surgery and CSF leak encouraged reoperation. Among the spontaneous spine and lumbar puncture-related CSF leaks, 57.1% of them responded to 4 days of conservative treatment. Among the trauma-related CSF leaks, 90.9% of them required surgical repair. The demographic data and symptoms were similar in various groups of CSF leak. The symptom onset durations and treatment strategies were different. However, the recurrence rates were similar.