Epigenetic Regulation of the Expression of T Cell Stimulatory and Inhibitory Factors by Histone H3 Lysine Modification Enzymes and Its Prognostic Roles in Glioblastoma

Background@#This study aimed to identify the specific T cell co-stimulatory and co-inhibitory factors that play prognostic roles in patients with glioblastoma. Additionally, the unique histone H3 modification enzymes that regulate the expression levels of these specific costimulatory and co-inhibitory factors were investigated. @*Methods@#The medical records of 84 patients newly diagnosed with glioblastoma at our institution from January 2006 to December 2020 were retrospectively reviewed.Immunohistochemical (IHC) staining for T cell co-stimulatory factors (CD27, CD28, CD137, OX40, and ICOS), T cell co-inhibitory factors (CTLA4, PD1, PD-L1, TIM3, and CD200R), and histone H3 lysine modification enzymes (MLL4, RIZ, EZH1, NSD2, KDM5c, JMJD1a, UTX, and JMJD5) was performed on archived paraffin-embedded tissues obtained by biopsy or resection. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed for specific factors, which demonstrated causal relationships, in order to validate the findings of the IHC examinations. @*Results@#The mean follow-up duration was 27.5 months (range, 4.1–43.5 months). During this period, 76 patients (90.5%) died, and the mean OS was 19.4 months (95% confidence interval, 16.3–20.9 months). Linear positive correlations were observed between the expression levels of CD28 and JMJD1a (R2 linear = 0.982) and those of CD137 and UTX (R2 linear = 1.528). Alternatively, significant negative correlations were observed between the expression levels of CTLA4 and RIZ (R2 linear = −1.746) and those of PD-L1 and EZH1 (R2 linear = −2.118); relationships were confirmed by qRT-PCR. In the multivariate analysis, increased expression levels of CD28 (P = 0.042), and CD137 (P = 0.009), and decreased expression levels of CTLA4 (P = 0.003), PD-L1 (P = 0.020), and EZH1 (P = 0.040) were significantly associated with longer survival. @*Conclusion@#These findings suggest that the expression of certain T cell co-stimulatory factors, such as CD28 and CD 137, and co-inhibitory factors, such as CTLA4 and PD-L1 are associated with prognosis of glioblastoma patients.

Role of Neurosurgeons in the Treatment of Acute Ischemic Stroke in the Emergency Room

Objective@#: With the recent increase in mechanical thrombectomy (MT) for acute ischemic stroke (AIS), the role of neurosurgeons in AIS treatment has become increasingly important. This study aimed to assess the outcomes of patients with AIS treated by neurosurgeons and neurologists in the emergency room (ER) of a tertiary hospital in South Korea. @*Methods@#: From January 2020 to June 2021, 536 patients with AIS within 24 hours of symptom onset were admitted to our hospital via the ER. Based on the type of doctors who provided initial care for AIS in the ER, patients were divided into two groups : (a) neurosurgeon group (n=119, 22.2%) and (b) neurologist group (n=417, 77.8%). @*Results@#: Intravenous tissue plasminogen activator (tPA) was administered in 82 (15.3%) of 536 patients (n=17 [14.3%] in the neurosurgeon group and n=65 [15.6%] in the neurologist group). The door-to-tPA time was not significantly different between both groups (median, 53 minutes; interquartile range [IQR], 45–58 vs. median, 54 minutes; IQR, 46–74; p=0.372). MT was performed in 69 patients (12.9%) (n=25, 36.2% in the neurosurgeon group and n=44, 63.8% in the neurologist group). The neurosurgeon group achieved a shorter door-to-puncture time than the neurologist group (median, 115 minutes; IQR, 107–151 vs. median, 162 minutes; IQR, 117–189; p=0.049). Good clinical outcomes (3-month modified Rankin Scale 0–2) did not differ significantly between the two groups (96/119 [80.7%] vs. 322/417 [77.2%], p=0.454). @*Conclusion@#: The neurosurgeon group showed similar door-to-treatment time and clinical outcomes to the neurologist group in patients with AIS in the ER. This study suggests that neurosurgeons have comparable abilities to care for patients with AIS in the ER.

Impact of the Coronavirus Disease Pandemic on Patients with Head Injuries in South Korea

Objective@#: The coronavirus disease 2019 (COVID-19) pandemic is affecting the characteristics of patients with head injuries. This study aimed to evaluate the effect of the COVID-19 pandemic on patients with head injuries at a regional emergency medical center in South Korea. @*Methods@#: From April 2019 to November 2020, 350 patients with head injuries were admitted to our hospital. The study period was divided into the pre-COVID-19 (n=169) and COVID-19 (n=181) eras (10 months each). Patients with severe head injuries requiring surgery (n=74) were categorized into those who underwent surgery (n=41) and those who refused surgery (n=33). @*Results@#: Head injuries in pediatric patients (<3 years) were more frequent in the COVID-19 era than in the pre-COVID-19 era (8.8% vs. 3.6%, p=0.048). More patients refused surgery in the COVID-19 era than in the pre-COVID-19 era (57.9% vs. 30.6%, p=0.021). Refusal of surgery was associated with old age (67.7±14.5 vs. 52.4±19.1, p<0.001), marital status (married, 84.8% vs. 61.0%, p=0.037), unemployment (42.4% vs. 68.3%, p=0.034), COVID-19 era (66.7% vs. 39.0%, p=0.021), and lower Glasgow coma scale scores (6.12±3.08 vs. 10.6±3.80, p<0.001). Multivariable logistic regression analysis revealed that refusal of surgery was independently associated with old age (adjusted odds ratio [OR], 1.084; 95% confidence interval [CI], 1.030–1.140; p=0.002), COVID-19 era (adjusted OR, 6.869; 95% CI, 1.624–29.054; p=0.009), and lower Glasgow coma scale scores (adjusted OR, 0.694; 95% CI, 0.568–0.848; p<0.001). @*Conclusion@#: We observed an increased prevalence of head injuries in pediatric patients (<3 years) during the COVID-19 pandemic. Additionally, among patients with severe head injuries requiring surgery, more patients refused to undergo surgery during the COVID-19 pandemic.

Comparative Analysis of the Patients with Spontaneous Thalamic Hemorrhage with Concurrent Intraventricular Hemorrhage and Those without Intraventricular Hemorrhage

Background@#This study aimed to compare the characteristics of patients with spontaneous thalamic hemorrhage (STH) accompanied by intraventricular hemorrhage (IVH) with those of patients without IVH. @*Methods@#The medical records of consecutive patients with STH admitted to our institute between January 2000 and December 2018 were reviewed retrospectively. The laboratory and radiological results, mortality, and functional recovery were compared between the STH patients with IVH and those without IVH. @*Results@#Among 2,389 patients with spontaneous intracerebral hemorrhage, 233 (9.8%) patients were included in this study. Concurrent IVH was detected in 159 (68.2%) patients with STH, and more frequently in those with body mass index ≥ 25, Glasgow Coma Scale score of 3–8, underlying disease, family history of stoke, posterior/medial/global location of hematoma, ventriculomegaly, large volume of hemorrhage, and midline shift ≥ 5 mm. The 3-month mortality was 25.8% and 8.1% (P = 0.039), the rate of good functional recovery at 6 months was 52.2% and 31.0% (P = 0.040), and incidence of delayed normal pressure hydrocephalus (NPH) at 12 months was 10.8% and 24.5% (P = 0.062) in the STH patients with IVH and those without IVH, respectively. At 12 months, delayed NPH developed in 28 of 47 (59.6%) patients who received external ventricular drainage (EVD)-based treatment, 5 of 45 (11.1%) patients who underwent endoscopic evacuation-based treatment, and 8 of 45 (17.8%) patients who underwent other surgeries. @*Conclusion@#Concurrent IVH is strongly associated with mortality in patients with STH. Delayed NPH may develop more frequently in STH patients with IVH who were treated with EVD.

A Meta-analysis for Evaluating Efficacy of Neuroendoscopic Surgery versus Craniotomy for Supratentorial Hypertensive Intracerebral Hemorrhage

OBJECTIVE: Hypertensive intracerebral hemorrhage is a potentially life-threatening neurological deficit with the highest morbidity and mortality. In recent years, neuroendoscopy has been used to treat intracerebral hemorrhages (ICHs). However, the choice of neuroendoscopic surgery or craniotomy for patients with ICHs is controversial. The objective of this meta-analysis was to assess the efficacy of neuroendoscopic surgery compared to craniotomy in patients with supratentorial hypertensive ICH.MATERIALS AND METHODS: A systematic electronic search was performed using online electronic databases such as Pubmed, Embase, and Cochrane library updated on December 2017. The meta-analysis was performed by only including studies designed as randomized controlled trials.RESULTS: Three randomized controlled trials met our inclusion criteria. Pooled analysis of death showed that neuroendoscopic surgery decreased the rate of death compared to craniotomy (RR=0.58, 95% CI: 0.26–1.29; P=0.18). Pooled results of complications showed that neuroendoscopic surgery tended to have fewer complications than craniotomy had (RR=0.37, 95% CI: 0.28–0.49; P < 0.0001).CONCLUSION: Although the presenting analyses suggest that neuroendoscopic surgery should have fewer complications than craniotomy dose, it had no superior advantage in morbidity rate definitely. Therefore, it may be necessary for the neurosurgeons to select best optimal patients for individual treatment.

Modified Arachnoid Plasty Reduces Chronic Subdural Hematoma after Unruptured Aneurysm Clipping : Technical Note

OBJECTIVE: Chronic subdural hematoma (CSDH) is a rare complication of unruptured intracranial aneurysm (UIA) clipping surgery. To prevent postoperative CSDH by reducing subdural fluid collection, we applied the modified arachnoid plasty (MAP) during the UIA clipping surgery to seal the dissected arachnoid plane.METHODS: This retrospective study included 286 patients enrolled from July 2012 to May 2015. We performed arachnoid plasty in all patients, with MAP used after June 17, 2014. Patients were divided into two groups (non-MAP vs. MAP), and by using uni- and multivariate analyses, baseline characteristics, and relationships with postoperative CSDH between the two groups were analyzed. The degree of preoperative brain atrophy was estimated using the bicaudate ratio (BCR) index.RESULTS: Ten patients (3.5%) among 286 patients had postoperative CSDH after clipping. Nine (3.1%) were in the non-MAP group, and one (0.9%) was in the MAP group. The higher BCR index showed statistical significance with occurrence of postoperative CSDH in both uni- (p=0.018) and multivariate (p=0.012; odds ratio [OR], 8.547; 95% confidence interval [CI], 1.616–45.455) analyses. MAP was associated with a lower risk of postoperative CSDH (p=0.022; OR, 0.068; 95% CI, 0.007–0.683).CONCLUSION: This study shows that the degree of preoperative brain atrophy is associated with an increased occurrence of CSDH after clipping and that MAP could help reduce the risk of postoperative CSDH after unruptured aneurysm clipping via a lateral supraorbital approach.

Modified Arachnoid Plasty Reduces Chronic Subdural Hematoma after Unruptured Aneurysm Clipping : Technical Note

OBJECTIVE: Chronic subdural hematoma (CSDH) is a rare complication of unruptured intracranial aneurysm (UIA) clipping surgery. To prevent postoperative CSDH by reducing subdural fluid collection, we applied the modified arachnoid plasty (MAP) during the UIA clipping surgery to seal the dissected arachnoid plane. METHODS: This retrospective study included 286 patients enrolled from July 2012 to May 2015. We performed arachnoid plasty in all patients, with MAP used after June 17, 2014. Patients were divided into two groups (non-MAP vs. MAP), and by using uni- and multivariate analyses, baseline characteristics, and relationships with postoperative CSDH between the two groups were analyzed. The degree of preoperative brain atrophy was estimated using the bicaudate ratio (BCR) index. RESULTS: Ten patients (3.5%) among 286 patients had postoperative CSDH after clipping. Nine (3.1%) were in the non-MAP group, and one (0.9%) was in the MAP group. The higher BCR index showed statistical significance with occurrence of postoperative CSDH in both uni- (p=0.018) and multivariate (p=0.012; odds ratio [OR], 8.547; 95% confidence interval [CI], 1.616–45.455) analyses. MAP was associated with a lower risk of postoperative CSDH (p=0.022; OR, 0.068; 95% CI, 0.007–0.683). CONCLUSION: This study shows that the degree of preoperative brain atrophy is associated with an increased occurrence of CSDH after clipping and that MAP could help reduce the risk of postoperative CSDH after unruptured aneurysm clipping via a lateral supraorbital approach.

Pure Subdural Hemorrhage Caused by Internal Carotid Artery Dorsal Wall Aneurysm Rupture

A 37-year-old woman was admitted to our hospital with altered mentality. The patient was diagnosed an internal carotid artery (ICA) dorsal wall aneurysm leading to acute subdural hemorrhage (SDH) without occurring subarachnoid hemorrhage and/or internal parenchymal hemorrhage. An aneurysmal neck clipping and hematoma evacuation were performed at once. A pure SDH by ruptured aneurysm is unusual, but it is important to consider it if a SDH patient has no other medical history.

Coronary Heart Disease in Moyamoya Disease: Are They Concomitant or Coincidence?

The purpose of this study was to determine the prevalence and characteristics of symptomatic coronary heart disease (CHD) in patients with moyamoya disease (MMD). This retrospective study evaluated 456 patients who received examination for MMD between 1995 and 2012. We reviewed the patients' medical history and coronary imaging, including conventional coronary angiography and coronary computed tomography angiogram (CTA). Among 456 patients with MMD, 21 (4.6%) patients were found to have symptomatic CHD. Ten patients were treated with coronary artery bypass graft or percutaneous coronary intervention for unstable angina or myocardial infarction. Eleven were treated with medication for stable angina (n = 6) and variant angina with mild degree of stenosis (n = 5).The median age of these patients was 44 yr (range, 27-59). The median Framingham score at diagnosing MMD was < 1% (range, < 1%-16%). The old age was associated with CHD in uni- and multivariate analyses (P = 0.021, OR, 1.053; 95% CI, 1.008-1.110). Considering low age of onset and low stroke risk factor, CHD might be a systemic manifestation that is clinically relevant to MMD.