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 co-stimulatory 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); these 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.

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.

Association of Aortic Arch Calcification on Chest X-ray with Procedural Thromboembolism after Mechanical Thrombectomy for Acute Ischemic Stroke.

Background and Objective: Procedural thromboembolism after a mechanical thrombectomy (MT) for an acute ischemic stroke (AIS) has rarely been studied. It may occur from the artery-to-artery embolization of atherosclerotic plaque in the aortic arch. We investigated the relationship between aortic arch calcification (AoAC) on a chest X-ray and procedural thromboembolism on diffusion-weighted imaging (DWI) after an MT. Materials and Methods: From January 2017 to December 2020, 131 patients underwent DWI within two days following an MT for an AIS. Procedural thromboembolism was defined as new DWI-positive lesions in other territories from the occluded artery on DWI within two days after MT. Results: Procedural thromboembolism was observed in 30 (22.9%) patients. Procedural thromboembolism was associated with old age (72.3 ± 9.44 vs. 65.7 ± 12.8 years, p = 0.003), a longer procedural time (77.6 ± 37.6 vs. 60.1 ± 29.7 min, p = 0.024), and AoAC (calcification (73.3%) vs. no calcification (29.7%), p < 0.001). Multivariable logistic regression analysis showed that procedural thromboembolism was independently associated with AoAC (adjusted odds ratio (OR): 6.107, adjusted 95% confidence interval (CI): 2.374-15.705, p < 0.001) and a longer procedural time (adjusted OR: 1.015, adjusted 95% CI: 1.001-1.030, p = 0.031). Conclusions: Procedural thromboembolism after an MT for an AIS was related to AoAC on a chest X-ray and a longer procedural time. Our results suggest that although rapid recanalization is the most crucial goal of an MT for an AIS, the importance of the careful advance of the guiding catheter through the aortic arch should not be underestimated to reduce the risk of procedural thromboembolism, especially in patients with AoAC on a chest X-ray.

Factors Associated with Procedural Thromboembolisms after Mechanical Thrombectomy for Acute Ischemic Stroke.

Background and objective: Procedural thromboembolisms after mechanical thrombectomy (MT) for acute ischemic stroke has rarely been studied. We retrospectively evaluated factors associated with procedural thromboembolisms after MT using diffusion-weight imaging (DWI) within 2 days of MT. Materials and Methods: From January 2018 to March 2020, 78 patients with acute ischemic stroke who underwent MT were evaluated using DWI. Procedural thromboembolisms were defined as new cerebral infarctions in other territories from the occluded artery on DWI after MT. Results: Procedural thromboembolisms were observed on DWI in 16 patients (20.5%). Procedural thromboembolisms were associated with old age (73.8 ± 8.18 vs. 66.8 ± 11.2 years, p = 0.021), intravenous (IV) thrombolysis (12 out of 16 (75.0%) vs. 25 out of 62 (40.3%), p = 0.023), heparinization (4 out of 16 (25.0%) vs. 37 out of 62 (59.7%), p = 0.023), and longer procedural time (90.9 ± 35.6 vs. 64.4 ± 33.0 min, p = 0.006). Multivariable logistic regression analysis revealed that procedural thromboembolisms were independently associated with procedural time (adjusted odds ratio (OR); 1.020, 95% confidence interval (CI); 1.002-1.039, p = 0.030) and IV thrombolysis (adjusted OR; 4.697, 95% CI; 1.223-18.042, p = 0.024). The cutoff value of procedural time for predicting procedural thromboembolisms was ≥71 min (area under the curve; 0.711, 95% CI; 0.570-0.851, p = 0.010). Conclusions: Procedural thromboembolisms after MT for acute ischemic stroke are significantly associated with longer procedural time and IV thrombolysis. This study suggests that patients with IV thrombolysis and longer procedural time (≥71 min) are at a higher risk of procedural thromboembolisms after MT for acute ischemic stroke.

Recent Trends in the Withdrawal of Life-Sustaining Treatment in Patients with Acute Cerebrovascular Disease : 2017-2021.

OBJECTIVE: The Act on Life-Sustaining Treatment (LST) decisions for end-of-life patients has been effective since February 2018. An increasing number of patients and their families want to withhold or withdraw from LST when medical futility is expected. This study aimed to investigate the status of the Act on LST decisions for patients with acute cerebrovascular disease at a single hospital. METHODS: Between January 2017 and December 2021, 227 patients with acute cerebrovascular diseases, including hemorrhagic stroke (n=184) and ischemic stroke (n=43), died at the hospital. The study period was divided into the periods before and after the Act. RESULTS: The duration of hospitalization decreased after the Act was implemented compared to before (15.9±16.1 vs. 11.2±18.6 days, p=0.127). The rate of obtaining consent for the LST plan tended to increase after the Act (139/183 [76.0%] vs. 27/44 [61.4%], p=0.077). Notably, none of the patients made an LST decision independently. Ventilator withdrawal was more frequently performed after the Act than before (52/183 [28.4%] vs. 0/44 [0%], p<0.001). Conversely, the rate of organ donation decreased after the Act was implemented (5/183 [2.7%] vs. 6/44 [13.6%], p=0.008). Refusal to undergo surgery was more common after the Act was implemented than before (87/149 [58.4%] vs. 15/41 [36.6%], p=0.021) among the 190 patients who required surgery. CONCLUSION: After the Act on LST decisions was implemented, the rate of LST withdrawal increased in patients with acute cerebrovascular disease. However, the decision to withdraw LST was made by the patient's family rather than the patient themselves. After the execution of the Act, we also observed an increased rate of refusal to undergo surgery and a decreased rate of organ donation. The Act on LST decisions may reduce unnecessary treatments that prolong end-of-life processes without a curative effect. However, the widespread application of this law may also reduce beneficial treatments and contribute to a decline in organ donation.

AGEs Blocker™ (Goji Berry, Fig, and Korean Mint Mixed Extract) Inhibits Skin Aging Caused by Streptozotocin-Induced Glycation in Hairless Mice.

Glycation is a cause of skin aging. This study investigated in a glycation-induced skin aging mouse model the effects on skin and mechanism of action of AGEs Blocker™ (AB), which contains goji berry, fig, and Korean mint mixed extract. This study sought to demonstrate the antiglycation effect of streptozotocin, thereby improving skin aging, by measuring advanced glycation end products (AGEs) and various skin parameters, including collagen; matrix metalloproteinases (MMPs); inflammatory cytokines; activities of oxidative enzymes; and skin wrinkles, elasticity, and hydration. This study found that skin wrinkles, elasticity, and hydration improved with AB. Particularly, the oral administration of AB suppressed AGEs, receptors of AGEs, and carboxymethyl lysine in blood and skin tissue. In addition, AB increased the activities of antioxidative enzymes, reduced inflammatory cytokines, suppressed MMP-9 expression, and increased the contents of collagen and hyaluronic acid, ultimately suppressing skin wrinkles and increasing skin elasticity and hydration. Therefore, AB can inhibit skin aging through its antiglycation effect and is thus considered a good ingredient for skin care products.

Clinical Application of the Association between Genetic Alteration and Intraoperative Fluorescence Activity of 5-Aminolevulinic Acid during the Resection of Brain Metastasis of Lung Adenocarcinoma.

The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM of lung adenocarcinoma at our institute for five years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.

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 on Endovascular Thrombectomy for Acute Ischemic Stroke of Aortic Arch Calcification on Chest X-ray.

BACKGROUND: Vascular conditions can affect the recanalization rates after endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Chest radiography can assess the conditions of the aortic arch based on the presence or absence of aortic arch calcification (AoAC). The aim of this study was to investigate the relationship between AoAC on chest radiography and first-pass successful recanalization (modified thrombolysis in cerebral infarction 2b/3 after the first-pass). METHODS: We compared the rate of first-pass successful recanalization between patients with and without AoAC. A total of 193 patients with anterior circulation occlusion who underwent EVT between January 2017 and December 2021 were included. RESULTS: AoAC was observed in 80 (41.5%) patients. Patients with AoAC were older (74.5 ± 7.78 vs. 63.9 ± 12.4 years, p < 0.001), had more EVT attempts (3.04 ± 1.95 vs. 2.01 ± 1.34 times, p < 0.001), and a longer procedural time (71.7 ± 31.2 vs. 48.7 ± 23.1 min, p < 0.001) than those without AoAC. Moreover, Patients with AoAC showed a lower incidence of first-pass successful recanalization (18.8% vs. 47.8%, p < 0.001) and a higher incidence of postprocedural hemorrhage (45.0% vs. 27.7%, p = 0.015) than those without AoAC. On multivariate analysis, AoAC was independently associated with first-pass successful recanalization (odds ratio: 0.239 [0.121-0.475], p < 0.001). CONCLUSIONS: AoAC on chest radiography can be used as a preoperative predictor of successful first-pass recanalization in patients undergoing EVT for AIS.

Effect of Antiplatelet Preparation Before Endovascular Thrombectomy for Cerebral Infarction on Procedural Thromboembolism.

AIM: To compare an antiplatelet-preparation group with a no-preparation group to evaluate the effect of the antiplatelet preparation on procedural thromboembolism during endovascular thrombectomy (EVT) with diffusion-weighted imaging (DWI), retrospectively. MATERIAL AND METHODS: From January 2017 to April 2020, EVT was performed in 60 patients with cerebral infarction. Patients were categorized into the antiplatelet-preparation group (n=25) or the no-preparation group (n=35). Procedural thromboembolism was defined as new DWI-positive lesions in other areas of the occluded artery after EVT. RESULTS: The antiplatelet-preparation and no-preparation groups did not differ in the rate of procedural thromboembolism occurrence (6/25 [24.0%] vs. 6/35 [17.1%]; p=0.532). Procedural thromboembolism was associated with age (74.4 ± 6.95 years vs. 65.7 ± 12.9 years; p=0.028), atherosclerotic occlusion (66.7% vs. 29.2%; p=0.022), and procedural time (97.4 ± 45.7 min vs. 60.1 ± 28.8 min; p=0.001). Multivariable logistic regression analysis showed that factors affecting procedural thromboembolism during EVT for cerebral infarction were old age (odds ratio [OR], 1.133; 95% confidence interval [CI], 1.009-1.273; p=0.035), atherosclerotic occlusion (OR, 7.434; 95% CI, 1.272-43.431; p=0.026), and longer procedural time (OR, 1.023; 95% CI, 1.001 - 1.046; p=0.006). CONCLUSION: The antiplatelet preparation had no significant protective effect on procedural thromboembolism during EVT for cerebral infarction. Old age, atherosclerotic occlusion, and longer procedural time were independent risk factors for procedural thromboembolism during EVT for cerebral infarction.

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.

Diffusion-weighted imaging-positive lesions following endovascular treatment for ruptured and unruptured aneurysms: Its incidence according to antithrombotic drugs.

OBJECTIVE: Microembolic infarcts are frequently observed on diffusion-weighted imaging (DWI) following endovascular treatment. We investigated DWI-positive lesions and symptomatic ischemic complications (SICs) in patients with ruptured and unruptured aneurysms following coiling and the relationship between DWI-positive lesions and antithrombotic drugs. METHODS: Between January 2016 and December 2020, 83 patients underwent DWI within 48 h following endovascular treatment for ruptured (n=30) and unruptured (n=53) aneurysms. RESULTS: The overall rate of DWI-positive lesions was 55.4%. There were no significant differences in the occurrence rate (45.3% vs. 43.3%, p=1.000) and the number of lesions (2.7±4.6 vs. 4.0±5.3, p=0.237) between unruptured and ruptured aneurysms. SIC occurred more frequently in patients with ruptured aneurysms than unruptured ones (20.0% vs. 1.9%, p=0.015). The cutoff value of DWI-positive lesions for predicting SIC was 5 (sensitivity 100%, specificity 78.9%). The procedure time was significantly longer in patients with DWI-positive lesions ≥5 than those with DWI-positive lesions <5 (104.1±43.8 vs. 85.1±30.8 min, p=0.030). Patients with DWI-positive lesions <5 were more frequently observed in the postprocedural heparinization group than in the no heparinization group (85.7% vs. 58.5%, p=0.012). CONCLUSIONS: The incidence of DWI-positive lesions did not differ significantly between the ruptured and unruptured aneurysms. However, SIC occurred more frequently in patients with ruptured aneurysms. Longer procedure time is a risk factor for DWI-positive lesions, and postprocedural heparinization seems to reduce the incidence of DWI-positive lesions.

Association of aortic arch calcification on chest X-ray with procedural thromboembolism after coil embolization of cerebral aneurysm.

Procedural thromboembolism after coil embolization of a cerebral aneurysm can occur because of fragmented atherosclerotic plaques in the aortic arch. The purpose of this study was to investigate the relationship between aortic arch calcification (AoAC) observed using preoperative chest X-ray and procedural thromboembolisms after coil embolization of cerebral aneurysms. Between January 2019 and December 2020, 66 patients underwent coil embolization for cerebral aneurysms at our hospital. AoAC was assessed based on the presence of calcification using a preoperative chest X-ray. A procedural thromboembolism was defined as a new positive lesion on diffusion-weighted imaging within 7 days post-procedure. A procedural thromboembolism occurred in 34 (51.5%) patients. The thromboembolism was associated with AoAC (calcification [52.9%] vs. no calcification [6.3%], p < 0.001), aneurysm type (aneurysm with incorporated branches [63.9%] vs. sidewall aneurysm [36.7%], p = 0.047), and a longer procedural time (100.2 ± 34.1 min vs. 79.7 ± 24.9 min, p = 0.007). Multivariable logistic regression analysis showed that AoAC (adjusted odds ratio [OR], 23.566; adjusted 95% confidence interval [CI], 3.921-141.654; p = 0.001) and aneurysm type (adjusted OR, 5.501; adjusted 95% CI, 1.455-20.799; p = 0.012) were independent risk factors for procedural thromboembolism. AoAC on preoperative chest X-ray was associated with a significant increase in the procedural thromboembolism rate. Our study suggests that a procedural thromboembolism after coil embolization of cerebral aneurysms might result primarily from fragmented atherosclerotic plaques in the aortic arch. Preoperative chest X-ray could be a useful tool to predict the risk of procedural thromboembolisms.

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.

Improving Door-To-Puncture Time in Mechanical Thrombectomy with Direct Care from a Neurointerventionalist in the Emergency Department.

OBJECTIVE: A shorter door-to-puncture time is an independent predictor of good clinical outcomes in patients with acute ischemic stroke (AIS) who undergo mechanical thrombectomy (MT). We recently initiated a protocol for direct care from neurointerventionalists (NIs) in the emergency department (ED) rather than from non-NI neurologists for patients with AIS. Our aim was to investigate whether NIs, as the first point-of-care physicians for stroke in the ED, could shorten door-to-puncture time compared to non-NI neurologists. METHODS: From January 2020 to December 2020, 50 patients with AIS underwent MT at our hospital. Patients were divided into 2 groups based on the type of physician who provided initial care for stroke in the ED: (a) NI group (n = 20) and (b) non-NI group (n = 30). The door-to-puncture time was retrospectively analyzed. RESULTS: The NI group had a significantly shorter door-to-puncture time than the non-NI group (135.2 ± 50.0 minutes vs. 167.2 ± 54.3 minutes, P = 0.040). A door-to-puncture time of ≤120 minutes was more frequently achieved in the NI group than in the non-NI group (55.0% vs. 23.3%, P = 0.022). Multivariable logistic regression analysis revealed that a door-to-puncture time of ≤120 minutes was independently associated with the NI group (adjusted odds ratio 4.098, 95% confidence interval 1.085-15.479, P = 0.037). CONCLUSIONS: Our study showed that NIs, as the first point-of-care stroke physicians in the ED, were associated with shorter door-to-puncture times. We suggest that NIs should be at the forefront of care for patients with AIS in the acute setting by performing triage and deciding on and performing MT.

Comparative Analysis of Stroke Patients with and without Sequelae: A Cross-Sectional Analysis Using the KOREA National Health and Nutrition Examination Survey (2016-2019).

(1) Background: We aimed to evaluate the association between sociodemographic factors and mental health problems and the sequelae of stroke in South Korea by analyzing the annual Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2016 to 2019. (2) Methods: Data were obtained from 32,379 participants who participated in the KNHANES (2016-2019). A total of 567 participants diagnosed with stroke were included in this study. Patients were divided into two groups based on the presence of sequelae: (a) stroke patients with sequelae (n = 227, 40.0%) and (b) stroke patients without sequelae (n = 340, 60.0%). (3) Results: Compared to stroke patients without sequelae, those with sequelae were significantly associated with sex (male, 61.2% vs. 47.6%, p = 0.002), household income (lower half, 78.9% vs. 67.4%, p = 0.005), owning a house (60.4% vs. 68.5%, p = 0.048), marital status (unmarried, 7.05% vs. 1.76%, p < 0.001), depression (13.2% vs. 7.35%, p = 0.045), suicidal ideation (6.17% vs. 3.24%, p = 0.010), and suicide attempts (2.64% vs. 0.88%, p = 0.012). (4) Conclusions: Our study showed that poor sociodemographic factors and mental health problems were significantly associated with sequelae from stroke. Clinical physicians should therefore carefully screen for depression and suicidality in stroke patients with sequelae, especially in those with poor sociodemographic factors.

Increased expression of the histone H3 lysine 4 methyltransferase MLL4 and the histone H3 lysine 27 demethylase UTX prolonging the overall survival of patients with glioblastoma and a methylated MGMT promoter.

OBJECTIVE The purpose of the present study was to investigate the epigenetic and prognostic roles of an H3K4 methyltransferase (mixed lineage leukemia 4 [MLL4]) and H3K27 demethylase (ubiquitously transcribed tetratricopeptide repeat gene on X chromosome [UTX]) in progression-free survival (PFS) and overall survival (OS) of patients with glioblastoma (GBM) who were treated with radiotherapy, chemotherapy, or both after resection. In addition, the authors examined methylation at the promoter of the O-6-methylguanine-DNA methyltransferase ( MGMT) gene and other prognostic factors predicting length of PFS and OS in these patients. METHODS The medical records of 76 patients having a new diagnosis of histologically ascertained GBM in the period of January 2002 to December 2013 at the authors' institution were retrospectively reviewed. Immunohistochemical staining for MLL4 and UTX was performed on archived paraffin-embedded tissues obtained by biopsy or resection. The methylation status of the MGMT promoter in these tissues was determined by methylation-specific PCR analysis. RESULTS During the follow-up period (mean length 18.1 months, range 4.1-43.5 months), 68 (89.5%) of the patients died. The MGMT promoter was methylated in 49 patients (64.5%) and unmethylated in 27 (35.5%). The immunoreactivity pattern of UTX was identical to that of MLL4; increased expression of these 2 proteins was observed in samples from 34 patients (44.7%) and decreased expression in 42 patients (55.3%). The mean length of PFS was 9.2 months (95% CI 6.8-11.6 months). Extent of surgery, recursive partitioning analysis (RPA) class, and methylation status of the MGMT promoter were all associated with increased PFS in the multivariate analysis of factors predicting PFS. The mean length of OS was 18.6 months (95% CI 14.3-22.9 months). Patient age (p = 0.004), WHO performance status score (p = 0.019), extent of surgery (p = 0.007), RPA class (p = 0.036), methylation status of the MGMT promoter (p = 0.010), and increased expression of UTX-MLL4 (p = 0.001) were significantly associated with increased OS in multivariate analysis. Interestingly, in patients with an unmethylated MGMT promoter, immunoreactivity of UTX-MLL4 was not associated with changes in OS (p = 0.350). However, in the patients with a methylated MGMT promoter, increased UTX-MLL4 expression was strongly associated with increased OS (p < 0.001). CONCLUSIONS The results of this study suggest that increased expression of UTX-MLL4 positively influences the outcome of patients with GBM having a methylated MGMT promoter. Therefore, UTX-MLL4 immunoreactivity could be a useful predictor of the response to conventional treatment with radiotherapy or chemotherapy among GBM patients whose tumors have a methylated MGMT promoter.

Function of cell-cycle regulators in predicting silent pituitary adenoma progression following surgical resection.

The present study investigated the use of cell-cycle regulators for predicting the progression of silent pituitary adenoma (SPA) following surgical resection, via immunohistochemical analysis of tumor samples obtained by surgical resection. The medical records of patients diagnosed with SPA between January 2000 and December 2013 in the Samsung Changwon Hospital, Sungkyunkwan University School of Medicine (Changwon, South Korea) were reviewed. Immunohistochemical staining was performed on sections of the archived, paraffin-embedded tissues obtained by surgery, with all tissues stained for cell-cycle regulatory proteins p16, p15, p21, cyclin-dependent kinase (CDK)4, CDK6, retinoblastoma protein (pRb) and cyclin D1, as well as E3 ubiquitin-protein ligase mib1 (MIB-1) antigen and p53. The primary end-point was to investigate the expression of cell-cycle regulatory proteins in SPA. The secondary end-point was to estimate the progression-free survival of patients with SPA following surgical resection and to identify its association with the expression of cell-cycle regulatory proteins. Of the 127 SPA samples, 44 (34.6%) were from patients with progression during a mean follow-up period of 62.4 months (range, 24.2-118.9 months). Immunohistochemical overexpression was identified in 61 samples (48.0%) for p16, 38 samples (29.9%) for p15, 19 samples (15.0%) for p21, 49 samples (38.6%) for CDK4, 17 samples (13.4%) for CDK6, 57 samples (44.9%) for pRb and in 65 samples (51.2%) for cyclin D1. Multivariate analysis revealed that null cell adenoma [95% confidence interval (CI), 0.276-0.808], somatotroph SPAs (95% CI, 1.296-3.121), corticotroph SPAs (95% CI, 1.811-4.078), pluripotent SPAs (95% CI, 2.264-5.194), decreased expression of p16 (95% CI, 2.724-5.588), overexpression of pRb (95% CI, 2.557-5.333), cyclin D1 (95% CI, 1.894-4.122) and MIB-1 (95% CI, 1.561-4.133), increased mitotic index (95% CI, 1.228-4.079), increased p53 expression (95% CI, 1.307-4.065) and invasion into the cavernous sinus (95% CI, 3.842-7.502) predicted SPA progression following resection. The results of the present study suggested that specific cell-cycle regulators, including p16, cyclin D1 and pRb, were associated with SPA progression.

Surgical Results of Pure Endoscopic Endonasal Transsphenoidal Surgery for 331 Pituitary Adenomas: A 15-Year Experience from a Single Institution.

BACKGROUND: The aim of this study is to report the results of pure endoscopic endonasal transsphenoidal surgery (EETSS) for pituitary adenomas (PAs) and to evaluate the efficacy and safety of this procedure. In addition, we tried to determine the predicting factors for progression of PAs. METHODS: We reviewed the medical records of 331 consecutive patients who underwent pure EETSS of newly diagnosed PAs between April 1998 and December 2014. Demographic, endocrinologic, and radiologic features and their outcomes, complications, and hospital stay durations were retrospectively assessed in these patients. RESULTS: There were 157 (47.4%) nonfunctioning adenomas and 174 (52.6%) hormone-secreting adenomas. Fifty-one (15.4%) complications were present in 39 patients postoperatively. The frequent complications were temporary and permanent diabetes insipidus (14 and 3 cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (9 cases), and cerebrospinal fluid leaks (6 cases). There was only 1 death (0.3%) related to the procedure in this series. The patient's age (P = 0.047), the tumor size (P = 0.003), and the parasellar growth (P <0.001) were associated with the occurrence of complications on multivariate analysis. Progression occurred in 92 (27.8%) patients and the mean time-to-progression was 23.7 months (range, 3.7-52.4 months) after a mean follow-up period of 68.5 months. In the multivariate analysis, the tumor size (P = 0.021), the extent of surgery (P = 0.012), the Knosp classification (P = 0.002), and the MIB-1 index (P = 0.019) were associated with progression-free survival. The mean duration of hospitalization was 4.4 (±1.6) days. CONCLUSIONS: The pure EETSS of PA provides acceptable and reasonable results representing a safe alternative procedure to the traditional transsphenoidal microscopic approach.

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.