Can Evoked Potential Changes during the Superficial Temporal Artery-Middle Cerebral Artery Bypass Surgery Predict Postoperative Improvement of Cerebral Perfusion and Functional Status?

BACKGROUND: We investigated evoked potential (EP) changes during superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery and their correlations with imaging and clinical findings postoperatively. METHODS: This retrospective study included patients who underwent STA-MCA bypass surgery due to ischemic stroke with large artery occlusion (MB group). Patients who underwent unruptured MCA aneurysm clipping were enrolled in the control group (MC group). Median and tibial somatosensory evoked potentials (SSEP), and motor evoked potentials recorded from the abductor pollicis brevis (APB-MEP) and abductor hallucis (AH-MEP) were measured intraoperatively. Modified Rankin scale (mRS) and perfusion-weighted imaging (PWI) related variables, i.e., mean transit time (MTT) and time to peak (TTP), were assessed. RESULTS: Δmedian SSEP, ΔAPB-MEP, and ΔAH-MEP were significantly higher in the MB group than in the MC group (p = 0.027, p = 0.006, and p = 0.015, respectively). APB-MEP and AH-MEP amplitudes were significantly increased at the final measurement (p = 0.010 and p < 0.001, respectively). The ΔTTP asymmetry index was moderately correlated with ΔAPB-MEP (r = 0.573, p = 0.005) and ΔAH-MEP (r = 0.617, p = 0.002). ΔAPB-MEP was moderately correlated with ΔMTT (r = 0.429, p = 0.047) and ΔmRS at 1 month (r = 0.514, p = 0.015). CONCLUSIONS: MEP improvement during STA-MCA bypass surgery was partially correlated with PWI and mRS and could reflect the recovery in cerebral perfusion.

Machine Learning-Based Three-Month Outcome Prediction in Acute Ischemic Stroke: A Single Cerebrovascular-Specialty Hospital Study in South Korea.

BACKGROUND: Functional outcomes after acute ischemic stroke are of great concern to patients and their families, as well as physicians and surgeons who make the clinical decisions. We developed machine learning (ML)-based functional outcome prediction models in acute ischemic stroke. METHODS: This retrospective study used a prospective cohort database. A total of 1066 patients with acute ischemic stroke between January 2019 and March 2021 were included. Variables such as demographic factors, stroke-related factors, laboratory findings, and comorbidities were utilized at the time of admission. Five ML algorithms were applied to predict a favorable functional outcome (modified Rankin Scale 0 or 1) at 3 months after stroke onset. RESULTS: Regularized logistic regression showed the best performance with an area under the receiver operating characteristic curve (AUC) of 0.86. Support vector machines represented the second-highest AUC of 0.85 with the highest F1-score of 0.86, and finally, all ML models applied achieved an AUC > 0.8. The National Institute of Health Stroke Scale at admission and age were consistently the top two important variables for generalized logistic regression, random forest, and extreme gradient boosting models. CONCLUSIONS: ML-based functional outcome prediction models for acute ischemic stroke were validated and proven to be readily applicable and useful.

Statin in combination with cisplatin makes favorable tumor-immune microenvironment for immunotherapy of head and neck squamous cell carcinoma.

The purpose of this study was to determine whether statins can enhance anticancer effects in head and neck squamous cell carcinoma (HNSCC) when used with cisplatin and act as immunogenic cell death (ICD) inducers that can be used in cancer immunotherapy. Statins alone showed both in vitro and in vivo inhibitory effects against HNSCC, and synergistic antitumor effects were observed when combined with cisplatin in a syngeneic murine HNSCC model. Statins increased calreticulin exposure and endoplasmic reticulum stress-related signals in HNSCC cells. In addition, it was confirmed that statins could activate antigen-presenting cells and tumor-specific CD8+ T cells with an increase in their numbers in the tumor tissues and draining lymph nodes, with this effect showing significant improvement following the combination therapy with cisplatin. Moreover, in triple combination with both cisplatin and anti-programmed cell death 1 receptor (anti-PD-1) antibody, statins dramatically induced further tumor eradication and improved the survival of tumor-bearing mice. Taken together, these results demonstrate that statins, administered in combination with anti-PD-1 antibody, could enhance the anticancer effect of cisplatin and potentiate the efficacy of immunotherapy for HNSCC and present a rationale for repurposing statins as an adjuvant immunotherapeutic option for HNSCC.

The Effects of Androstenone on the Plasma Serotonin, ß-Endorphin, and Cortisol Concentrations in Thoroughbred Horses.

Androstenone influences the changing behaviors of animals. Previous studies discovered that an androstenone receptor was expressed in horses and treatment with androstenone induced horses to be more compliant. As changes in the level of neuroendocrine factors result in animal behavioral changes, the objective of the study was to monitor the changes in the concentrations of 5-HT, ß-endorphin, and cortisol in response to androstenone. Eight thoroughbred horses (five mares and three geldings) were treated with androstenone diluted in jojoba oil (10 µg/mL) and only oil for a control cross-overly. A handler applied the treatments to the horses' nostril and rubbed for 5 s. Blood samples were collected before, 15, 30, and 60 min after each treatment. The concentrations of each neurotransmitter were analyzed by enzyme-linked immunosorbent assay. The concentrations of each neurotransmitter after the treatment were compared to its baseline concentration. The concentration of 5-HT of the androstenone-treated horses remained consistent throughout the experiment, while the concentration of the control group significantly decreased over time. The plasma concentration of ß-endorphin in the androstenone-treated group also remained constant, whereas the concentration increased in the control group. Cortisol levels did not change in either the treated or untreated groups. An androstenone treatment triggers changes in the secretion of 5-HT and ß-endorphin in horses.

Usefulness of Intraoperative Neurophysiological Monitoring During the Clipping of Unruptured Intracranial Aneurysm: Diagnostic Efficacy and Detailed Protocol.

Background: Intraoperative neurophysiological monitoring (IONM) has been widely applied in brain vascular surgeries to reduce postoperative neurologic deficit (PND). This study aimed to investigate the effect of IONM during clipping of unruptured intracranial aneurysms (UIAs). Methods: Between January 2013 and August 2020, we enrolled 193 patients with 202 UIAs in the N group (clipping without IONM) and 319 patients with 343 UIAs in the M group (clipping with IONM). Patients in the M group were intraoperatively monitored for motor evoked potentials (MEPs) and somatosensory evoked potentials (SSEPs). Irreversible evoked potential (EP) change was defined as EP deterioration that did not recover until surgery completion. Sustained PND was defined as neurological symptoms lasting for more than one postoperative month. Results: Ten (3.1%) and 13 (6.7%) in the M and N groups, respectively, presented with PND. Compared with the N group, the M group had significantly lower occurrence rates of sustained PND [odds ratio (OR) = 0.36, 95% confidence interval (CI) = 0.13-0.98, p = 0.04], ischemic complications (OR = 0.39, 95% CI = 0.15-0.98, p = 0.04), and radiologic complications (OR = 0.40, 95% CI = 0.19-0.82, p = 0.01). Temporary clipping was an independent risk factor for ischemic complications (ICs) in the total patient group (OR = 6.18, 95% CI = 1.75-21.83, p = 0.005), but not in the M group (OR = 5.53, 95% CI = 0.76-41.92, p = 0.09). Regarding PND prediction, considering any EP changes (MEP and/or SSEP) showed the best diagnostic efficiency with a sensitivity of 0.900, specificity of 0.940, positive predictive value of 0.321, negative predictive value (NPV) of 0.997, and a negative likelihood ratio (LR) of 0.11. Conclusion: IONM application during UIA clipping can reduce PND and radiological complications. The diagnostic effectiveness of IONM, specifically the NPV and LR negative values, was optimal upon consideration of changes in any EP modality.

Stage-Dependent Expression of Protein Gene Product 9.5 in Donkey Testes.

Molecular markers can be used to identify and isolate specific developmental stages of germ cells and Leydig cells. Protein gene product (PGP)9.5 expression in spermatogonia and Leydig cells has been reported in several species. The stages of spermatogonia and Leydig cells expressing PGP9.5 vary depending on the species and reproductive stages. Thus, the objectives of this study were (1) to identify the localization of PGP9.5 in donkey testicular cells, and (2) to compare the expression patterns of PGP9.5 in donkey testicular cells between pre- and post-pubertal stages. Testes samples were collected following the routine field castration of six donkeys. Western blotting was performed to verify the cross-reactivity of the rabbit anti-human PGP9.5 antibody to donkey testes. Immunofluorescence was performed to investigate the expression pattern of PGP9.5 in testicular tissues at different reproductive stages. In Western blotting, the protein band of the PGP9.5 antibody appeared at approximately 27 kDa, whereas the band was not observed in the negative control treated with normal mouse IgG. In the pre-pubertal stage, the expression of deleted in azoospermia-like (DAZL) was found in some spermatogonia in pre-pubertal testicular tissues. However, the immunolabeling of PGP9.5 in testicular tissue was not observed in the seminiferous tubules. In stages 1 and 2, spermatogonia were immunolabeled with either PGP9.5 or DAZL. In contrast, PGP9.5 and DAZL were co-immunolabeled in some of the spermatogonia in stages 3 to 8. Interestingly, some Leydig cells were immunolabeled with PGP9.5 in both pre- and post-pubertal stages. In conclusion, the PGP9.5 antibody can be used as a tool to identify and isolate spermatogonia from seminiferous tubules.

Effects of Zn-Doped Mesoporous Bioactive Glass Nanoparticles in Etch-and-Rinse Adhesive on the Microtensile Bond Strength.

The purpose of this study was to assess the effects in the dentin bond strength of dental adhesives (DAs) and biological effects using zinc (Zn)-doped mesoporous bioactive glass nanoparticles (MBN-Zn). Synthesized MBN and MBN-Zn were characterized by scanning electron microscopy (SEM), X-ray diffraction and the Brunauer, Emmett and Teller (BET) method. The matrix metalloproteinases (MMP) inhibition effects of DA-MBN and DA-MBN-Zn were analyzed. The microtensile bond strength (MTBS) test was conducted before and after thermocycling to investigate the effects of MBN and MBN-Zn on the MTBS of DAs. The biological properties of DA-MBN and DA-MBN-Zn were analyzed with human dental pulp stem cells (hDPSCs). Compared with the DA, only the DA-1.0% MBN and DA-1.0% MBN-Zn exhibited a statistically significant decrease in MMP activity. The MTBS values after thermocycling were significantly increased in DA-1.0% MBN and DA-1.0% MBN-Zn compared with the DA (p < 0.05). It was confirmed via the MTT assay that there was no cytotoxicity for hDPSCs at 50% extract. In addition, significant increases in the alkaline phosphatase activity and Alizarin Red S staining were observed only in DA-1.0%MBN-Zn. These data suggest the 1.0% MBN and 1.0% MBN-Zn enhance the remineralization capability of DAs and stabilize the long-term MTBS of DAs by inhibiting MMPs.

Immediate effects of mandibular posterior displacement on the pharyngeal airway space: A preliminary study.

OBJECTIVE: This study aimed to evaluate the immediate effects of mandibular posterior displacement on the pharyngeal airway space (PAS) by using cephalometric evaluations and to investigate how the surrounding structures are schematically involved. METHODS: In this retrospective study, 38 subjects with functional Class III malocclusion and two lateral cephalograms were selected. The first lateral cephalogram was taken with the mandible in the habitual occlusal position, and the second in anterior edge-to-edge bite. Paired t-test was used to analyze changes in the PAS, hyoid bone, tongue, and soft palate, followed by mandibular posterior displacement. Pearson's correlation analysis was used to determine the relationship between the amount of mandibular posterior displacement and other variables. RESULTS: A statistically significant decrease was observed in the PAS following mandibular posterior displacement. Along with mandibular posterior displacement, the tongue decreased in length (p < 0.001) and increased in height (p < 0.05), while the soft palate increased in length, decreased in thickness, and was posteriorly displaced (p < 0.001). The hyoid bone was also posteriorly displaced (p < 0.05). There was no correlation between the amount of mandibular posterior displacement and the measured variables. CONCLUSIONS: The PAS showed a statistically significant decrease following mandibular posterior displacement, which was a consequence of retraction of the surrounding structures. However, there were individual variances between the amount of mandibular posterior displacement and the measured variables.

In-Vitro Study of Urokinase Thrombolysis Following Stereotactic Aspiration of Intracerebral Hematoma.

OBJECTIVE: A consensus regarding the ideal regimen for urokinase (UK) thrombolysis subsequent to stereotactic spontaneous intracerebral hemorrhage aspiration has yet to be established. The purpose of this study is to evaluate the efficacy of UK thrombolysis relative to when the regimen is changed. METHODS: Venous blood from 30 heathy volunteers was obtained for this in-vitro study. Various concentrations of UK solution were added to microcentrifuge tubes containing the clotted blood. The efficacy of UK thrombolysis was identified by checking the weight of lysed hematoma following various time intervals with different concentrations of UK solution. Group one, the "3×4" group involved four administrations every 3 hours over 12 hours, and group two, the "6×2" group involved two administrations every 6 hours over 12 hours. RESULTS: More hematoma was lysed in the 3×4 group than the 6×2 group across all concentration levels (however, the differences were only significant between groups at the 500 and 1000 IU concentration levels, p<0.05). There were no significant differences of lysed hematoma among the various UK solution concentrations within groups. CONCLUSION: This study suggests that frequent administrations of UK thrombolysis may result in a greater degree of lysed hematoma in comparison to a higher concentration of UK.

Intraoperative Mannitol Administration Increases the Risk of Postoperative Chronic Subdural Hemorrhage After Unruptured Aneurysm Surgery.

OBJECTIVE: Although mannitol is used widely to facilitate brain retraction in cases of ruptured aneurysms, there is no consensus about the intraoperative administration of mannitol in the case of unruptured aneurysms. Accordingly, this study was conducted to identify an intraoperative mannitol administration strategy. METHODS: Mannitol was administered routinely to patients (n = 90) from January 2015 to April 2016 and not administered to patients (n = 97) from May 2016 to June 2017. The patient groups with and without mannitol administration were then compared based on the patient medical records, radiologic data, and digital recordings from an intraoperative microscope. RESULTS: The patient groups with and without mannitol administration were comparable regarding patient age, number of elderly patients, sex, and aneurysm locations. No between-group difference was identified in terms of the intradural procedural time, retraction-induced cortical injury, postoperative electrolyte imbalance, symptomatic infarction, and postoperative epidural hematomas. However, the patient group without mannitol administration showed a significantly lower incidence of chronic subdural hematomas (CSDHs) >50 mL (13.3% vs. 3.1%, P = 0.010). Moreover, a multivariate analysis revealed that an advanced age (P = 0.019), male sex (P <0.001), and mannitol administration (P = 0.040) were all statistically significant risk factors for a postoperative CSDH >50 mL following unruptured aneurysm surgery. CONCLUSIONS: Withholding the administration of mannitol during a pterional or modified procedure for unruptured aneurysms was found to reduce the postoperative occurrence of a CSDH without increasing the operative difficulties or other postoperative complications.

Cerebrospinal Fluid Leak at Percutaneous Exit of Ventricular Catheter as a Crucial Risk Factor for External Ventricular Drainage-Related Infection in Adult Neurosurgical Patients.

OBJECTIVE: The placement of a ventricular catheter for temporary cerebrospinal fluid (CSF) diversion is associated with a considerable risk of CSF infection. The authors investigated the effect of a CSF leak on CSF-related infection and the predisposing factors for a CSF leak. METHODS: Fifty-two patients who underwent external ventricular drainage (EVD) for acute hydrocephalus associated with a subarachnoid hemorrhage or intraventricular hemorrhage (IVH) were enrolled in this prospective study. A CSF leak-detection paper (small sterilized filter paper) was applied at the percutaneous catheter exit site to check for any bloody CSF leak. In addition, radiologic and clinical data were collected. RESULTS: Four of the 52 patients (7.7%) developed an EVD-related CSF infection from organisms including Staphylococcus epidermidis (n = 3) and Staphylococcus hominis (n = 1). A prolonged CSF leak >1 day was detected in 9 patients (17.3%) and revealed as a significant risk factor for CSF infection with a 44.4% positive predictive value. Moreover, an IVH >10 mL was found in 11 patients (21.2%) and revealed as a significant predisposing factor for a CSF leak at the percutaneous catheter exit. CONCLUSIONS: A prolonged CSF leak for >1 day at the percutaneous catheter exit site is a crucial risk factor for EVD-related CSF infection and an IVH >10 mL is a predisposing factor for a CSF leak.

Traumatic Brain Injury in Children under Age 24 Months: Analysis of Demographic Data, Risk Factors, and Outcomes of Post-traumatic Seizure.

OBJECTIVE: Traumatic brain injury (TBI) in children under age 24 months has characteristic features because the brain at this age is rapidly growing and sutures are opened. Moreover, children this age are completely dependent on their parents. We analyzed the demographic data and risk factors for outcomes in TBI patients in this age group to elucidate their clinical characteristics. METHODS: We retrospectively reviewed the medical records and radiological films of children under 24 months who were admitted to Kyungpook National University Hospital from January 2004 to December 2013 for TBI. Specifically, we analyzed age, cause of injury, initial Glasgow coma scale (GCS) score, radiological diagnosis, seizure, hydrocephalus, subdural hygroma, and Glasgow outcome scale (GOS) score, and we divided outcomes into good (GOS 4-5) or poor (GOS 1-3). We identified the risk factors for post-traumatic seizure (PTS) and outcomes using univariate and multivariate analyses. RESULTS: The total number of patients was 60, 39 males and 21 females. Most common age group was between 0 to 5 months, and the median age was 6 months. Falls were the most common cause of injury (n=29, 48.3%); among them, 15 were falls from household furniture such as beds and chairs. Ten patients (16.7%) developed PTS, nine in one week; thirty-seven patients (61.7%) had skull fractures. Forty-eight patients had initial GCS scores of 13-15, 8 had scores of 12-8, and 4 had scored 3-7. The diagnoses were as follows: 26 acute subdural hematomas, 8 acute epidural hematomas, 7 focal contusional hemorrhages, 13 subdural hygromas, and 4 traumatic intracerebral hematomas larger than 2 cm in diameter. Among them, two patients underwent craniotomy for hematoma removal. Four patients were victims of child abuse, and all of them had PTS. Fifty-five patients improved to good-to-moderate disability. Child abuse, acute subdural hematoma, and subdural hygroma were risk factors for PTS in univariate analyses. Multivariate analysis found that the salient risk factor for a poor outcome was initial GCS on admission. CONCLUSION: The most common cause of traumatic head injury in individuals aged less than 24 months was falls, especially from household furniture. Child abuse, moderate to severe TBI, acute subdural hematoma, and subdural hygroma were risk factors for PTS. Most of the patients recovered with good outcomes, and the risk factor for a poor outcome was initial mental status.

Intradural Procedural Time to Assess Technical Difficulty of Superciliary Keyhole and Pterional Approaches for Unruptured Middle Cerebral Artery Aneurysms.

OBJECTIVE: This study used the intradural procedural time to assess the overall technical difficulty involved in surgically clipping an unruptured middle cerebral artery (MCA) aneurysm via a pterional or superciliary approach. The clinical and radiological variables affecting the intradural procedural time were investigated, and the intradural procedural time compared between a superciliary keyhole approach and a pterional approach. METHODS: During a 5.5-year period, patients with a single MCA aneurysm were enrolled in this retrospective study. The selection criteria for a superciliary keyhole approach included : 1) maximum diameter of the unruptured MCA aneurysm <15 mm, 2) neck diameter of the MCA aneurysm <10 mm, and 3) aneurysm location involving the sphenoidal or horizontal segment of MCA (M1) segment and MCA bifurcation, excluding aneurysms distal to the MCA genu. Meanwhile, the control comparison group included patients with the same selection criteria as for a superciliary approach, yet who preferred a pterional approach to avoid a postoperative facial wound or due to preoperative skin trouble in the supraorbital area. To determine the variables affecting the intradural procedural time, a multiple regression analysis was performed using such data as the patient age and gender, maximum aneurysm diameter, aneurysm neck diameter, and length of the pre-aneurysm M1 segment. In addition, the intradural procedural times were compared between the superciliary and pterional patient groups, along with the other variables. RESULTS: A total of 160 patients underwent a superciliary (n=124) or pterional (n=36) approach for an unruptured MCA aneurysm. In the multiple regression analysis, an increase in the diameter of the aneurysm neck (p<0.001) was identified as a statistically significant factor increasing the intradural procedural time. A Pearson correlation analysis also showed a positive correlation (r=0.340) between the neck diameter and the intradural procedural time. When comparing the superciliary and pterional groups, no statistically significant between-group difference was found in terms of the intradural procedural time reflecting the technical difficulty (mean±standard deviation : 29.8±13.0 min versus 27.7±9.6 min). CONCLUSION: A superciliary keyhole approach can be a useful alternative to a pterional approach for an unruptured MCA aneurysm with a maximum diameter <15 mm and neck diameter <10 mm, representing no more of a technical challenge. For both surgical approaches, the technical difficulty increases along with the neck diameter of the MCA aneurysm.

Two cases of cavernous malformation presenting with unusual and large intracerebral hemorrhages.

Cavernous malformations (CMs), characterized by the presence of a hemosiderin rim and intralesional hemorrhage, are relatively common intracranial vascular malformations. Extralesional hemorrhages arising from CMs are seen in a minority of cases, but most of them show typical CM findings on magnetic resonance imaging. Here, the authors report two cases of pathologically confirmed CM presenting with unusual and large intracerebral hemorrhages, which were not surrounded by the typical hemosiderin rim. CMs presenting with large intracerebral hemorrhage should be considered in the differential diagnosis of massive intracerebral hemorrhages.

Ectopic expression of apple MbR7 gene induced enhanced resistance to transgenic Arabidopsis plant against a virulent pathogen.

A disease resistance related gene, MbR7, was identified in the wild apple species, Malus baccata. The MbR7 gene has a single open reading frame (ORF) of 3,288 nucleotides potentially encoding a 1,095-amino acid protein. Its deduced amino acid sequence resembles the N protein of tobacco and the NL27 gene of potato and has several motifs characteristic of a TIR-NBS-LRR R gene subclass. Ectopic expression of MbR7 in Arabidopsis enhanced the resistance against a virulent pathogen, Pseudomonas syringae pv. tomato DC3000. Microarray analysis confirmed the induction of defense-related gene expression in 35S::MbR7 heterologous Arabidopsis plants, indicating that the MbR7 gene likely activates a downstream resistance pathway without interaction with pathogens. Our results suggest that MbR7 can be a potential target gene in developing a new disease-resistant apple variety.