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.

Stent-assisted Coil Embolization of Petrous ICA in a Teenager with Neurofibromatosis

We herein report on a patient with a cerebral aneurysm located at the petrous portion of the internal carotid artery (ICA). An 18-year-old male, previously diagnosed with neurofibromatosis, was referred to our emergency service complaining of severe headache, pulsatile tinnitus, nausea, and vomiting which occurred suddenly. Neuro-radiological studies including computed tomography and magnetic resonance imaging of the cerebral artery showed a large aneurysm arising from the petrous segment of the left ICA. He was treated with a neuro-interventional technique such as intra-arterial stenting and coil embolization for the aneurysm. Several days after the interventional treatment, his symptoms were resolved gradually except for a mild headache. Symptomatic unruptured aneurysm at the petrous portion of the ICA is rare, and our patient was treated successfully using a neuro-intervention technique. Therefore, we describe a case of a petrous aneurysm treated with endovascular coils without compromising the ICA flow, and review the literature.

What Should Be Considered to Cause the Early Post-Craniotomy Seizure: Antibiotics (Cefazolin) Irrigation

OBJECTIVE: Post-craniotomy seizure (PCS) is reported only rarely. However, our department noted a 433% increase in PCS for a year beginning September 2010, especially after cerebrovascular surgery. Our goal was to identify the cause of our unusual outbreak of PCS. METHODS: For almost one year after September 2010, cases of PCS increased significantly in our department. We analyzed 973 patients who had received a major craniotomy between January 2009 and November 2011. We included seizures that occurred only in the first 24 postoperative hours, which we defined as early PCS. After verifying the presence of PCS, we analyzed multiple seizure-provoking factors and their relation to the duration and character of seizure activity. RESULTS: Overall PCS incidence was 7.2% (70/973). Cefazolin (2 g/L saline) was the antibiotic drug used for intraoperative irrigation in 88.4% of the operations, and no PCS occurred without intraoperative cefazolin irrigation. When analyzed by operation type, clipping surgery for unruptured aneurysms was the most frequently associated with PCS (80%). Using logistic regression, only 2 g cefazolin intraoperative irrigation (p=0.024) and unruptured aneurysm clipping surgery (p<0.001) were associated with early PCS. The seizure rate of unruptured aneurysm clipping surgery using 2 g cefazolin intraoperative irrigation was 32.9%. CONCLUSION: Intraoperative cefazolin irrigation must be avoided in patients undergoing craniotomy, especially for clipping of unruptured aneurysms, because of the increased risk of early PCS.

Pontomedullary Laceration, a Fatal Consequence of Skull Base Ring Fracture

Due to improvements in emergency resuscitation provided by rescue teams, more trauma victims who could have died due to sudden heart failure at the scene are brought to the hospital following resuscitation. Most of these patients present with major organ injuries and hypovolemic shock at the time of trauma. However, head trauma associated with sudden heart arrest is rare. Here, we report a case of ring fracture with pontomedullary laceration that led to sudden heart arrest.

Therapeutic Hypothermia after Decompressive Craniectomy in Malignant Cerebral Infarction / 대한구급학회지

Decompressive hemicraniectomy followed by subsequent therapeutic hypothermia can reduce mortality in patients with malignant cerebral infarction without significantly increasing risk. We report three cases of malignant cerebral infarction treated with hemicraniectomy followed by hypothermia. Case 1 received elective decompressive surgery and hypothermia. Case 2 developed subsequent cerebral infarction with uncal herniation. Therefore, emergent decompressive surgery and hypothermia was performed in this case. Despite surgery and hyperosmolar therapy, case 3 received hypothermia treatment for refractory increased intracranial pressure. All patients survived with a score of 4 or 5 on the modified Rankin scale. Therefore, we suggest that application of hypothermia after hemicraniectomy is safe and feasible. Several possible modifications can be made to improve the management strategy in order to increase the benefits of hypothermia treatment.

Predictors of 30-day Mortality and 90-day Functional Recovery after Primary Pontine Hemorrhage

The factors related to death and functional recovery after primary pontine hemorrhage (PPH) in Koreans has not been well defined. The authors sought to identify independent predictors of death and functional recovery after PPH using data obtained at a single institute. Data were collected retrospectively on 281 patients with PPH admitted to the Stroke Unit at our hospital between January 1, 2000 and December 31, 2009. Multivariate logistic regression analysis was used to evaluate the associations between selected variables and 30-day mortality and 90-day functional recovery after PPH. One-hundred and ten patients (39.1%) died within 30 days of PPH and 27 patients (9.6%) achieved functional recovery within 90 days. By multivariate analysis, unconsciousness, dilated pupils, abnormal respiration, systolic blood pressure < 100 mmHg, hydrocephalus, and conservative treatment were found to be predictors of 30-day mortality, whereas consciousness, intact motor function, no history of hypertension or diabetes mellitus, intact eye movement, a hematoma volume of < 5 mL, no ventricular hemorrhage, and normally sized ventricle were found to be predictors of 90-day functional recovery. The present findings suggest that systolic hypotension of less than 100 mmHg may predict 30-day mortality and a history of underlying hypertension and diabetes mellitus may predict 90-day functional recovery.