Assessment of Risks and Benefits of Using Antibiotics Resistance Genes in Mesenchymal Stem Cell-Based Ex-Vivo Therapy

Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (PuroR) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo, we generated a puromycin-resistant

Preclinical Study on Biodistribution of Mesenchymal Stem Cells after Local Transplantation into the Brain

Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo.Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals.After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.

Introduction of Multidisciplinary Team Approach for Head and Neck Cancer: Patient Satisfaction / 대한이비인후과학회지

Background and Objectives@#The head and neck multidisciplinary team (MDT) approach plays a crucial role in bringing together the ideas of various medical professionals. This study aimed to evaluate the early characteristics of the MDT approach for head and neck cancer and analyzed patients’ satisfaction.Subjects and Method We analyzed 450 head and neck cancer patients who received MDT care from August 2014 to June 2022. Patient satisfaction with MDT care was evaluated by selfadministered questionnaires consisting of 9 questions. @*Results@#Of 450, 298 (66.2%) were male and 152 (33.8%) were female. The mean age was 60.8±14.7 year. The most common primary site was the larynx (17.3%), followed by the oral cavity and oropharynx. A total of 726 cases of the MDT approach were performed in 266 MDT sessions, and the mean number of patients per MDT session was 2.74. The number of medical professionals participating in MDT ranged from a minimum of 3 to a maximum of 9, with a mean of 5.11. The mean running time of MDT meetings per case was 19.51 minutes. The time of the 2nd MDT was significantly shorter than that of the 1st or 3rd MDT. The mean score was close to very satisfactory in each of the 9 patient satisfaction questions. @*Conclusion@#We believe that the MDT approach is feasible and recommend its introduction for the treatment of head and neck cancer as most patients have shown very high satisfaction. Further studies on the role and efficacy of MDT care for head and neck cancer are necessary.

Monitoring Radiation Doses during Diagnostic and Therapeutic Neurointerventional Procedures: Multicenter Study for Establishment of Reference Levels / 신경중재치료의학

Purpose@#To assess patient radiation doses during diagnostic and therapeutic neurointerventional procedures from multiple centers and propose dose reference level (RL). @*Materials and Methods@#Consecutive neurointerventional procedures, performed in 22 hospitals from December 2020 to June 2021, were retrospectively studied. We collected data from a sample of 429 diagnostic and 731 therapeutic procedures. Parameters including dose-area product (DAP), cumulative air kerma (CAK), fluoroscopic time (FT), and total number of image frames (NI) were obtained. RL were calculated as the 3rd quartiles of the distribution. @*Results@#Analysis of 1160 procedures from 22 hospitals confirmed the large variability in patient dose for similar procedures. RLs in terms of DAP, CAK, FT, and NI were 101.6 Gy·cm2, 711.3 mGy, 13.3 minutes, and 637 frames for cerebral angiography, 199.9 Gy·cm2, 3,458.7 mGy, 57.3 minutes, and 1,000 frames for aneurysm coiling, 225.1 Gy·cm2, 1,590 mGy, 44.7 minutes, and 800 frames for stroke thrombolysis, 412.3 Gy·cm2, 4,447.8 mGy, 99.3 minutes, and 1,621.3 frames for arteriovenous malformation (AVM) embolization, respectively. For all procedures, the results were comparable to most of those already published. Statistical analysis showed male and presence of procedural complications were significant factors in aneurysmal coiling. Male, number of passages, and procedural combined technique were significant factors in stroke thrombolysis. In AVM embolization, a significantly higher radiation dose was found in the definitive endovascular cure group. @*Conclusion@#Various RLs introduced in this study promote the optimization of patient doses in diagnostic and therapeutic interventional neuroradiology procedures. Proposed 3rd quartile DAP (Gy·cm2) values were 101.6 for diagnostic cerebral angiography, 199.9 for aneurysm coiling, 225.1 for stroke thrombolysis, and 412.3 for AVM embolization. Continual evolution of practices and technologies requires regular updates of RLs.

Microbleeds in the Corpus Callosum in Anoxic Brain Injury

Purpose@#This study was performed to evaluate the relationship between callosal microbleeds and anoxic brain injury. @*Materials and Methods@#Twenty-seven patients with anoxic brain injuries were analyzed and retrospectively compared to the control group of patients without a history of anoxic brain injury using Fisher's exact test regarding comorbidities and cerebral microbleeds. The patient group was subdivided according to the presence of callosal microbleeds. Fisher's exact test was used to compare the presence of typical MRI findings of anoxic brain injury, use of cardiopulmonary resuscitation, and prognosis. The Mann-Whitney U test was used to compare the interval between the occurrence of anoxic brain injury to MRI acquisition. @*Results@#The prevalence of cerebral microbleeds in the patient group was 29.6%, which was significantly higher than that in the control group at 3.7% (p = 0.012). All cerebral microbleeds in the patient group were in the corpus callosum. Compared with the callosal microbleed-absent group, the callosal microbleed-present group showed a tendency of good prognosis (6/8 vs. 11/19), fewer typical MRI findings of anoxic brain injury (2/8 vs. 10/19), and more cardiopulmonary resuscitation (6/8 vs. 12/19), although these differences did not reach statistical significance (p = 0.35, p = 0.19, and p = 0.45, respectively). @*Conclusion@#Callosal microbleeds may be an adjunctive MRI marker for anoxic brain injury.

Recent Trend for Endovascular Treatment in Patients with Acute Ischemic Stroke: Balloon Guide Catheter / 신경중재치료의학

No abstract available.

Diffusion Tensor Imaging and Quantitative Magnetic Resonance Volumetric Assessment in the Diagnosis of Hemimegalencephaly: A Case Report

A 27-year-old female presented with repeated seizures. As the left frontal lobe volume was enlarged in comparison with the right frontal lobe, hemimegalencephaly was suggested. Abnormal white matter fiber tracts running from the left frontal lobe to the fornix and hippocampus were found on diffusion tensor imaging (DTI). We performed quantitative measurements of brain volume and confirmed hemimegalencephaly. DTI and MRI-based volumetry techniques could be useful to objectively diagnose hemimegalencephaly.

Size Reduction of an Intracranial Aneurysm after Resolution of Vasospasm: A Case Report

Vasospasm after subarachnoid hemorrhage may alter intracranial hemodynamics. We report a case which showed significant size reduction of an unruptured intracranial aneurysm after resolution of vasospasm. This case may suggest that aneurysm size can be affected by vasospasm, which is presumably related to changes in hemodynamics or spontaneous thrombosis.

Risk Factors of Delayed Surgical Intervention after Conservatively Treated Acute Traumatic Subdural Hematoma

OBJECTIVE: Acute subdural hematoma (ASDH) is generally considered a condition that should be managed surgically. However, some patients initially receive conservative treatment, a subset of whom require surgical intervention later. This study aimed to evaluate the predictors of delayed surgical intervention in ASDH patients who are initially managed conservatively. METHODS: From January 2007 to December 2015, 842 patients diagnosed with ASDH were treated at our institution. Among them, 158 patients with convexity ASDH were initially treated conservatively. Patients were divided into a delayed surgery group and a conservative group. Demographic characteristics, past medication and medical histories, and radiological and laboratory data were collected by retrospective chart review. Independent risk factors were identified with univariate and multivariate analyses. RESULTS: Twenty-eight patients (17.7%) underwent delayed surgical intervention. Their mean age was 69.0 years, and 82.1% were male. Hypertension, diabetes mellitus, and heart disease prevalence and use of anti-platelet agents did not significantly differ from the conservative group. However, age (p=0.024), previous cerebral infarction history (p=0.026), increased maximal hematoma thickness (p<0.001), midline shifting (p=0.001) and accompanying subarachnoid hemorrhage (p=0.022) on initial brain computed tomography (CT) scan, low hemoglobin level (p<0.001), high leukocyte count (p=0.004), and low glucose level (p=0.002) were significantly associated with delayed surgical intervention. In multivariate analysis, increased maximal hematoma thickness (odds ratio [OR]=1.279, 95% confidence interval [CI] 1.075–1.521; p=0.006), low hemoglobin level (OR=0.673, 95% CI 0.467–0.970; p=0.034), and high leukocyte count (OR=1.142, 95% CI 1.024–1.272; p=0.017) were independent risk factors for delayed surgical intervention. CONCLUSION: Due to the high likelihood of delayed surgical intervention among minimal ASDH patients with a thicker hematoma on initial brain CT, lower hemoglobin level, and higher leukocyte count, these patients should receive more careful observation.

Patient Radiation Exposure During Diagnostic and Therapeutic Procedures for Intracranial Aneurysms: A Multicenter Study / 신경중재치료의학

PURPOSE: To assess patient radiation doses during cerebral angiography and embolization of intracranial aneurysms across multi-centers and propose a diagnostic reference level (DRL). MATERIALS AND METHODS: We studied a sample of 490 diagnostic and 371 therapeutic procedures for intracranial aneurysms, which were performed at 23 hospitals in Korea in 2015. Parameters including dose-area product (DAP), cumulative air kerma (CAK), fluoroscopic time and total angiographic image frames were obtained and analyzed. RESULTS: Total mean DAP, CAK, fluoroscopy time, and total angiographic image frames were 106.2 ± 66.4 Gy-cm2, 697.1 ± 473.7 mGy, 9.7 ± 6.5 minutes, 241.5 ± 116.6 frames for diagnostic procedures, 218.8 ± 164.3 Gy-cm², 3365.7 ± 2205.8 mGy, 51.5 ± 31.1 minutes, 443.5 ± 270.7 frames for therapeutic procedures, respectively. For diagnostic procedure, the third quartiles for DRLs were 144.2 Gy-cm² for DAP, 921.1 mGy for CAK, 12.2 minutes for fluoroscopy times and 286.5 for number of image frames, respectively. For therapeutic procedures, the third quartiles for DRLs were 271.0 Gy-cm² for DAP, 4471.3 mGy for CAK, 64.7 minutes for fluoroscopy times and 567.3 for number of image frames, respectively. On average, rotational angiography was used 1.5 ± 0.7 times/session (range, 0-4; n=490) for diagnostic procedures and 1.6 ± 1.2 times/session (range, 0-4; n=368) for therapeutic procedures, respectively. CONCLUSION: Radiation dose as measured by DAP, fluoroscopy time and image frames were lower in our patients compared to another study regarding cerebral angiography, and DAP was lower with fewer angiographic image frames for therapeutic procedures. Proposed DRLs can be used for quality assurance and patient safety in diagnostic and therapeutic procedures.

Oncologists' Experience with Patients with Second Primary Cancer and the Attitudes toward Second Primary Cancer Screening: A Nationwide Survey / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Screening for second primary cancer (SPC) is one of the key components to survivorship care. We aim to evaluate the oncologists' experience with SPCs and assess the current practice, perceived barriers, and recommendations related to SPC screening. MATERIALS AND METHODS: A nationwide survey was conducted with a representative sample of 496 Korean oncologists. A questionnaire based on the findings from our previous qualitative study was administered. RESULTS: More than three-fourths of oncologists (76.3%), who participated in the study, had experience with SPC patients. Over half of them (51.9%) stated that it was an embarrassing experience. While the current management practice for SPC varies, most oncologists (80.2%) agreed on the necessity in proactively providing information on SPC screening. A short consultation time (52.3%), lack of guidelines and evidence on SPC screening (47.7%), and patients' lack of knowledge about SPCs (45.1%) or SPC screening (41.4%) were most frequently reported as barriers to providing appropriate care for managing SPC. Oncologists recommended the development of specific screening programs or guidelines in accordance to the type of primary cancer (65.9%), the development of an internal system for SPC screening within the hospital (59.7%) or systematic connection with the national cancer screening program (44.3%), and education of oncologists (41.4%) as well as patients (48.9%) regarding SPC screening. CONCLUSION: Many oncologists reported the occurrence of SPC as an embarrassing experience. Given the variations in current practice and the lack of consensus, further studies are warranted to develop the optimal clinical strategy to provide SPC screening for cancer survivors.

Delayed Cerebral Hyperperfusion Syndrome Three Weeks after Carotid Artery Stenting Presenting as Status Epilepticus

Cerebral hyperperfusion syndrome (CHS) is increasingly recognized as an uncommon, but serious, complication subsequent to carotid artery stenting (CAS) and carotid endarterectomy (CEA). The onset of CHS generally occurs within two weeks of CEA and CAS, and a delay in the onset of CHS of over one week after CAS is quite rare. We describe a patient who developed CHS three weeks after CAS with status epilepticus.

Facial Palsy and Nystagmus after Transvenous Embolization of a Carotid Cavernous Fistula / 대한뇌졸중학회지

No abstract available.

Efficacy of Entecavir Switching Therapy in Chronic Hepatitis B Patients with Clevudine-induced Myopathy / 대한소화기학회지

BACKGROUND/AIMS: Clevudine is a potent antiviral agent against HBV. However, long-term clevudine therapy may cause myopathy. This study was carried out to identify the efficacy of entecavir switching therapy in chronic hepatitis B patients experiencing clevudine-induced myopathy. METHODS: One hundred forty six patients with chronic hepatitis B treated with 30 mg of clevudine per day for 73 weeks (range, 36-132 weeks) were enrolled. Among them, clevudine-induced myopathy occurred in 21 patients (14.4%) which was diagnosed if the patients had symptoms related to myopathy with concurrent CK and AST elevation. All the patients who were diagnosed as clevudine-induced myopathy stopped the therapy, and 17 patients (81%) were switched to entecavir 0.5 mg. RESULTS: The patients with clevudine-induced myopathy were switched to entecavir 0.5 mg for median 68 weeks, and all of them showed disappearance of clinical myopathic symptoms and normalization of CK and AST level within median 2.2 months. Eight patients (47%) were HBeAg positive before entecavir treatment, and HBeAg seroconversion was achieved in 2 patients (25%). HBV DNA level was elevated in 3 patients (17.6%) at the time when the patients were diagnosed as myopathy, all of them achieved virological response with entecavir switching therapy. ALT level was elevated in 3 patients (17.6%) before entecavir treatment, all of them showed normalization of ALT level. During entecavir therapy, genotypic resistance to entecavir or virological breakthrough was not noted. CONCLUSIONS: In chronic hepatitis B patients experiencing clevudine-induced myopathy, switching to entecavir 0.5 mg per day showed a resolution of myopathy and adequate viral suppression.

Pure Intrasellar Meningioma Located Under the Pituitary Gland: Case Report

Most intrasellar meningiomas are located in the subdiaphragmatic and supraglandular region because they originate from the diaphragma sellae. Subglandular meningiomas located under the pituitary gland are extremely rare. Intrasellar meningiomas in the subdiaphragmatic and subglandular region probably originate from the dura in the sellar floor. We report a case of a subglandular meningioma along with a review of the literature.

Multicenter clinical trial of leuprolide acetate depot (Luphere depot 3.75 mg) for efficacy and safety in girls with central precocious puberty

PURPOSE: We evaluated the efficacy, safety and psychological aspect of monthly administrations of the gonadotropin-releasing hormone agonists (GnRHa), leuprolide acetate depot (Luphere depot 3.75 mg), in patients with precocious puberty. METHODS: A total of 54 girls with central precocious puberty were administered with leuprolide acetate (Luphere depot 3.75 mg) every four weeks over 24 weeks. We evaluated the percentage of children exhibiting a suppressed luteinizing hormone (LH) response to GnRH (LH peak< or =3 IU/L), peak LH/follicle stimulating hormone (FSH) ratio of GnRH stimulation test less than 1, change in bone age/chronologic age ratio, change in the Tanner stage and change in eating habit and psychological aspect. RESULTS: (1) The percentage of children exhibiting a suppressed LH response to GnRH, defined as an LH peak< or =3 IU/L at 24 weeks was 96.3 % (52/54). (2) The percentage of children exhibiting peak LH/FSH ratio<1 at 24 weeks of the study was 94.4 % (51/54). (3) The ratio of bone age and chronological age significantly declined from 1.27+/-0.07 to 1.24+/-0.01 after the 6 months of the study. (4) The mean Tanner stage manifested a significant change 2.3+/-0.48 at baseline, down to 1.70+/-0.61 at 24 weeks. (5) Based on the questionnaires, the score for eating habits showed a significant change from the baseline 34.0+/-6.8 to 31.3+/-6.8. (6) The psychological assessment did not exhibit a significant difference except with scores for sociability, problem behavior total score and other problems. CONCLUSION: The leuprolide 3.75 mg (Luphere depot) is useful and safety for treating children with central precocious puberty.

Chronic Subdural Hematoma in Young Adult: An Age Comparison Study / 대한신경손상학회지

OBJECTIVE: Incidence of chronic subdural hematoma (CSDH) is gradually increasing in young adults for several reasons. In this study, we aimed to identify features of CSDH noted in young adults that distinguish the disease from CSDH diagnosed in the elderly. METHODS: One hundred eighty-two patients with CSDH who underwent a total of 218 surgical procedures between January 2003 and February 2010 were retrospectively reviewed with regard to clinical presentation, radiographic results and prognosis including recurrence. To compare younger patients with the elderly, patients were divided into three groups on the basis of age (Group A: or =65 years). RESULTS: Group A showed a male predominance (p=0.0001), lower rate of recurrence (p=0.0012), shorter symptom duration (p=0.035), and fewer leading signs such as hemispheric symptoms (p=0.005) compared to Groups B and C. Radiologic findings such as maximal hematoma thickness (p<0.0001) and degree of midline shift (p=0.028) were less severe in Group A than Groups B and C. Alcoholism was the most prevalent illness in all three groups. When exempting infants with hematologic malignancy, non-recurrence, previous trauma history, headache as leading symptom, and no mortality were all common in younger adults (all p<0.05). CONCLUSION: Young adults with CSDH show less severe clinical and radiologic features as well as fewer recurrences than noted in the elderly population. Even if a clinician's index of suspicion of CSDH in young adults complaining of headache is not high, meticulous radiologic surveillance could find CSDH, leading to satisfactory results including less frequent recurrence.

Spontaneous Anterior Cerebral Artery Dissection Presenting with Simultaneous Subarachnoid Hemorrhage and Cerebral Infarction in a Patient with Multiple Extracranial Arterial Dissections

Simultaneous subarachnoid hemorrhage and infarction is a quite rare presentation in a patient with a spontaneous dissecting aneurysm of the anterior cerebral artery. Identifying relevant radiographic features and serial angiographic surveillance as well as mode of clinical manifestation, either hemorrhage or infarction, could sufficiently determine appropriate treatment. Enlargement of ruptured aneurysm and progressing arterial stenosis around the aneurysm indicates impending risk of subsequent stroke. In this setting, prompt treatment with stent-assisted endovascular embolization can be a reliable alternative to direct surgery. When multiple arterial dissections are coexistent, management strategy often became complicated. However, satisfactory clinical results can be obtained by acknowledging responsible arterial site with careful radiographic inspection and antiplatelet medication.

A randomized, double-blind study to evaluate the efficacy of ramosetron and palonosetron for prevention of postoperative nausea and vomiting after gynecological laparoscopic surgery / 대한마취과학회지

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication after anesthesia and surgery; 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have been considered as a first-line therapy. Ramosetron and palonosetron are more recently developed drugs and have greater receptor affinity and a longer elimination half-life compared with older 5-HT3 receptor antagonists. The purpose of this study was to determine which drug is more effective for preventing PONV between ramosetron and palonosetron. METHODS: We enrolled 100 patients undergoing gynecological laparoscopic surgery into this study. The subjects were divided into ramosetron group and palonosetron group. The medications were provided immediately before the induction of anesthesia. The occurrence of nausea and vomiting, severity of nausea according to a visual analogue scale, and rescue anti-emetic drug use were monitored immediately after the end of surgery and at 0-6 h, 6-24 h, and 24-48 h post-surgery. RESULTS: The incidence of vomiting was significantly lower in the palonosetron group than in the ramosetron group during 0-6 h (6% vs 26%, P = 0.012) and 0-48 h (14% vs 34%, P = 0.034). The incidence of nausea and overall PONV, and the use of rescue antiemetic were not significantly different during all time intervals. The severity of nausea was not different between the two groups. CONCLUSIONS: In conclusion, the incidence of PONV between the ramosetron and the palonosetron group have not shown the difference during 0-48 h, although palonosetron results in a lower incidence of vomiting during 0-6 h post-surgery.

Nodular Hyperplasia Arising from the Lateral Aberrant Thyroid Tissue: A Case Report

The presence of aberrant thyroid tissue in the lateral neck is very rare. In addition, nodular hyperplasia in ectopic thyroid has rarely been reported. Due to the unusual location, the presence of lateral aberrant thyroid tissue could be misdiagnosed as a lymphadenopathy, neurogenic tumor, etc. We report on a case of nodular hyperplasia arising from the right lateral aberrant thyroid tissue.