Organ-Specific Differentiation of Human Adipose-Derived Stem Cells in Various Organs of Xenotransplanted Rats: A Pilot Study.

Adipose-derived stem cells (ADSCs) are potential therapeutics considering their self-renewal capacity and ability to differentiate into all somatic cell types in vitro. The ideal ADSC-based therapy is a direct injection into the relevant organs. The objective of this study was to investigate the viability and safety of intra-organ human ADSC (h-ADSC) xenotransplants in vivo. Subcutaneous adipose tissue from the abdominal area of 10 patients was sampled. h-ADSCs were isolated from adipose tissue samples and identified using immunofluorescence antibodies. Multi-differentiation potential assays for adipocytes, osteocytes, and chondrocytes were performed. Cultured h-ADSCs at passage 4 were transplanted into multiple organs of 17 rats, including the skin, subcutaneous layer, liver, kidney, pancreas, and spleen. The h-ADSC-injected organs excised after 100 days were examined, and the survival of h-ADSCs was measured by quantitative real-time polymerase chain reaction (qRT-PCR) using specific human and rat target genes. h-ADSCs confirmed by stem cell phenotyping were induced to differentiate into adipogenic, osteogenic, and chondrogenic lineages in vitro. All rats were healthy and exhibited no side effects during the study; the transplanted h-ADSCs did not cause inflammation and were indiscernible from the native organ cells. The presence of transplanted h-ADSCs was confirmed using qRT-PCR. However, the engrafted survival rates varied as follows: subcutaneous fat (70.6%), followed by the liver (52.9%), pancreas (50.0%), kidney (29.4%), skin (29.4%), and spleen (12.5%). h-ADSCs were successfully transplanted into a rat model, with different survival rates depending on the organ.

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.

Association of Family History with the Development of Breast Cancer: A Cohort Study of 129,374 Women in KoGES Data.

BACKGROUND: Breast cancer is the most common cancer among women. The Korean Genome and Epidemiology Study (KoGES) is a large cohort study that is available to the public. Using this large cohort study, we aimed to unravel the relationship between breast cancer development and a family history of breast cancer in Korea. METHODS: This cohort study relied on data from the KoGES from 2001 through 2013. A total of 211,725 participants were screened. Of these, 129,374 women were evaluated. They were divided into two groups, including participants with and without breast cancer. A logistic regression model was used to retrospectively analyze the odds ratio of breast cancer history in families of women with and without breast cancer. RESULTS: Of 129,374 women, 981 had breast cancer. The breast cancer group had more mothers and siblings with histories of breast cancer (p < 0.001). A history of breast cancer in the participant's mother resulted in an odds ratio of 3.12 (1.75-5.59), and a history of breast cancer in the participant's sibling resulted in an odds ratio of 2.63 (1.85-3.74). There was no interaction between the history of maternal breast cancer and the history of sibling breast cancer. Based on the subgroup analysis, family history was a stronger factor in premenopausal women than in menopausal and postmenopausal women. CONCLUSIONS: A family history of breast cancer is a significant risk factor for breast cancer in Korea. Premenopausal women with a maternal history of breast cancer are of particular concern. Intensive screening and risk-reducing strategies should be considered for this vulnerable subpopulation.

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.

Strategy to reduce unnecessary surgeries in thyroid nodules with cytology of Bethesda category III (AUS/FLUS): a retrospective analysis of 667 patients diagnosed by surgery.

PURPOSE: Fine-needle aspiration (FNA) is widely used for the diagnosis of thyroid nodules detected by ultrasonography. However, the cytology of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) often leads to unnecessary thyroid surgery. This study aimed to identify a strategy to reduce unnecessary surgeries in patients with AUS/FLUS nodules. METHODS: Medical records of 667 patients with the cytology of AUS/FLUS who underwent surgery from January 2007 to December 2017 were retrospectively reviewed. Clinicopathological data were analyzed to identify malignant factors in thyroid nodules with AUS/FLUS. Factors were compared between patients with thyroid cancer and those with benign thyroid nodules, using stepwise multivariate logistic regression and decision tree model. RESULTS: Pathological thyroid cancer was identified in 193 (43.3%) patients. There was a significant difference in malignancy incidence with respect to family history, number of nodules, number of FNAs, ultrasonographic finding, lymphocytic thyroiditis, and BRAFV600E mutation. Multivariate analysis showed that ultrasonography (K-TIRADS 5) was the most influential independent predictor of malignancy in AUS/FLUS (odds ratio = 11.02, p < 0.001), followed by possessing BRAFV600E mutation (odds ratio = 4.54, p < 0.001). This strategy enabled 226 (89.3%) patients to avoid unnecessary surgeries based on the decision tree model. There was no node of repeated FNA in the decision tree model, which reduced the risk of malignancy (odds ratio = 0.35, p = 0.029). CONCLUSION: K-TIRADS 5 and BRAFV600E mutation were predictive of malignancy in nodules of AUS/FLUS. These factors should be considered in strategies to reduce unnecessary surgeries for AUS/FLUS.

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.