Establishment of Neurotoxicity Assessment Using Microelectrode Array (MEA) with hiPSC-Derived Neurons and Evaluation of New Psychoactive Substances (NPS)

Background and Objectives@#Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. @*Methods@#and Results: In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. @*Conclusions@#Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.

Delayed Treatment of Iatrogenic Brachial Arteriovenous Fistula

Iatrogenic vascular injuries may occur during venipuncture, arterial cannulation, or catheterization procedures. Brachial arteriovenous fistula (AVF) resulting from antecubital vascular access is rare and develops slowly. We report the case of an 18-year-old man who had developed iatrogenic brachial AVF. He had a history of several venipunctures in the left arm at the age of 10 months. Doppler ultrasonography and computed tomographic angiography were used to establish a diagnosis of brachial AVF, and surgical correction of the AVF was performed. As our case indicates, delayed surgery can be considered as a treatment option and may be associated with a decreased risk of vascular complications in the management of iatrogenic brachial AVF in infants.

Serum Fibroblast Growth Factor 21 and New-Onset Metabolic Syndrome: KoGES-ARIRANG Study

PURPOSE: Fibroblast growth factor 21 (FGF21) is a crucial metabolic regulator, with multiple favorable effects on glucose homeostasis and lipid metabolism. Since serum FGF21 level has been implicated as a potential marker for the early identification of metabolic syndrome (MetS), we investigated the association between serum FGF21 level and the development of MetS in a population-based prospective study. MATERIALS AND METHODS: We conducted a prospective study of 221 randomly sampled adults without MetS from a general population-based cohort study who were examined from 2005–2008 (baseline) and from 2008–2011 (follow-up). Baseline serum FGF21 levels were analyzed using enzyme-linked immunosorbent assay. RESULTS: During the average 2.8-year follow-up period, 82 participants (36.6%) developed new-onset MetS. Serum FGF21 levels were significantly higher in patients with new-onset MetS than in those without MetS (209.56±226.80 vs. 110.09±81.10, p < 0.01). In multivariate adjusted models, the odds for MetS development were greater in patients with serum FGF21 levels in the highest quartile, compared to those in the lowest quartile (3.84, 95% confidence interval: 1.59–9.28). CONCLUSION: Serum FGF21 level was an independent predictor for new-onset MetS in a population-based prospective study.

Intermittent Claudication due to Cystic Adventitial Disease of the Popliteal Artery: Importance of Multiple Imaging Modalities

No abstract available.

Basiliximab-Induced Non-Cardiogenic Pulmonary Edema in a Kidney Transplant Patient / 대한이식학회지

Induction therapy with basiliximab is widely administered after kidney transplantation to prevent acute rejection. Herein, we report a case of non-cardiogenic pulmonary edema induced by basiliximab. To the best of our knowledge, such case has not been reported to date in Korea. A 54-year-old man with polycystic kidney disease received kidney transplantation. As induction therapy, he was prescribed basiliximab. On day 4, the second dose of basiliximab was administered. The patient complained of acute hypoxia 23 hours later, which led to circulatory collapse. He was discharged 3 weeks later with stable renal function. Pulmonary edema was presumed to have been caused by increased pulmonary capillary permeability. A possible hypothesis for this event occurring after the second basiliximab injection is steroid-related effects. Non-cardiogenic pulmonary edema is a complication that might occur after basiliximab induction therapy. Physicians should be aware of this potentially life-threatening complication.

Comparison of Anterior Translation among Three Sternoclavicular Reconstruction Methods in Cadaver Study / 대한정형외과학회잡지

PURPOSE: Currently, biomechanics and function comparison of the reconstruction of structures play important roles in the sternoclavicular joint stability is not much. In order to confirm the improvement in the functional aspects of the sternoclavicular joint after the three most widely used reconstruction methods, we measured the degree of anterior translation of the sternoclavicular joint after the operation using cadavers. MATERIALS AND METHODS: We studied 24 sternoclavicular joints in the cadavers. First, we measured the anterior translation of the clavicle, which was compared with the sternum in 24 normal sternoclavicular joints. We divided the cadaver into three groups and performed each of the three current operations: figure of eight hamastring tendon reconstruction operation (Group 1), subclavius tendon reconstruction operation (Group 2), and hamstring tendon reconstruction operation (Group 3); then we compared the degree of anterior translation in each group. We did the measurement by adding 10 degrees to the glenohumeral joint each time from 0 degrees to 90 degrees. RESULTS: In the normal joint, the clavicle was significantly ascended compared with the sternum. The Group 1 had a 1.68±0.25 mm anterior translation while the Group 2 had 1.81±0.23 mm and Group 3 had 2.8±0.58 mm (Group 1: p=0.004, Group 2: p=0.001, Group 3: p=0.002). The Group 1 showed a low ascending rate of up to 60 degrees, which showed no significant difference with that of the normal joint. However, after 60 degrees, the ascending rate showed a significant increase. In the case of Group 2, there was no significant difference with normal joint of up to 50 degrees. Group 3 showed significant anterior ascending from 20 degree. CONCLUSION: Through measuring the anterior translation of subjects that underwent three representative sternoclavicular joint reconstructions, we found that the result from the Group 1 was most comparable normal translation of the sternoclavicular joint.

Analysis of Sternal Fixation Results According to Plate Type in Sternal Fracture

BACKGROUND: Sternal fractures are relatively rare, and caused mainly by blunt anterior chest wall trauma. In most cases, sternal fractures are treated conservatively. However, if the patient exhibits problematic symptoms such as intractable chest wall pain or bony crepitus due to sternal instability, surgical correction is indicated. But no consensus exists regarding the most appropriate surgical method. We analyzed the results of surgical fixation in cases of sternal fracture in order to identify which surgical method led to the best outcomes. METHODS: We retrospectively reviewed the medical records of patients with sternal fractures from December 2008 to December 2011, and found 19 patients who underwent open reduction and internal fixation of the sternum with a longitudinal plate (L-group) or a T-shaped plate (T-group). We investigated patients' characteristics, clinical details regarding each case of chest trauma, the presence of other associated injuries, the type of open reduction and fixation, whether a combined operation was performed, and postoperative complications. RESULTS: Of the 19 patients, 10 patients (52.6%) were male, and their average age was 56.8 years (range, 32 to 82 years). Seven patients (36.8%) had isolated sternal fractures, while 12 (63.2%) had other associated injuries. Seven patients (36.8%) were in the L-group and 12 patients (63.2%) were in the T-group. Three patients in the L-group (42.9%) showed a loosening of the fixation. In all patients in the T-group, the fracture exhibited stable alignment. CONCLUSION: Open reduction and internal fixation with a T-shaped plate in sternal fractures is a safer and more efficient treatment method than treatment with a longitudinal plate, especially in patients with a severely displaced sternum or anterior flail chest, than a longitudinal plate.

Complications of Central Venous Totally Implantable Access Port: Internal Jugular Versus Subclavian Access / 대한구급학회지

BACKGROUND: Totally implantable access port (TIAP) provides reliable, long term vascular access with minimal risk of infection and allows patients normal physical activity. With wide use of ports, new complications have been encountered. We analyzed TIAP related complications and evaluated the outcomes of two different percutaneous routes of access to superior vena cava. METHODS: All 172 patients who underwent port insertion with internal jugular approach (Group 1, n = 92) and subclavian approach (Group 2, n = 79) between August 2011 and May 2013 in a single center were analyzed, retrospectively. Medical records were analyzed to compare the outcomes and the occurrence of port related complications between two different percutaneous routes of access to superior vena cava. RESULTS: Median follow-up for TIAP was 278 days (range, 1-1868). Twenty four complications were occurred (14.0%), including pneumothorax (n = 1, 0.6%), migration/malposition (n = 4, 2.3%), pinch-off syndrome (n = 4, 2.3%), malfunction (n = 2, 1.1%), infection (n = 8, 4.7%), and venous thrombosis (n = 5, 2.9%). The overall incidence was 8.7% and 20.3% in each group (p = 0.030). Mechanical complications except infectious and thrombotic complications were more often occurred in group 2 (p = 0.033). The mechanical complication free probability is significantly higher in group 1 (p = 0.040). CONCLUSIONS: We suggest that the jugular access should be chosen in patients who need long term catheterization because of high incidence of mechanical complication, such as pinch-off syndrome.

Cardiac Rupture of the Junction of the Right Atrium and Superior Vena Cava in Blunt Thoracic Trauma / 대한구급학회지

Cardiac rupture following blunt thoracic trauma is rarely encountered, since it commonly causes death at the scene. With advances in critical care, blunt cardiac rupture has been successfully treated with well-organized team approach including an emergency physician, anesthesiologist, and cardiac surgeon. We encountered a patient with blunt cardiac rupture of the junction of the superior vena cava and right atrium that extended 7 cm to the right ventricular junction. The patient was successfully resuscitated after a closed thoracostomy and pericardiocentesis with fluid loading. Cardiac injury was repaired via mid-sternotomy without cardiopulmonary bypass. The patient recovered without complications and was discharged on the 7th day after surgery.

Epidemiology of Trauma Patients and Analysis of 268 Mortality Cases: Trends of a Single Center in Korea

PURPOSE: There is an increasing incidence of mortality among trauma patients; therefore, it is important to analyze the trauma epidemiology in order to prevent trauma death. The authors reviewed the trauma epidemiology retrospectively at a regional emergency center of Korea and evaluated the main factors that led to trauma-related deaths. MATERIALS AND METHODS: A total of 17007 trauma patients were registered to the trauma registry of the regional emergency center at Wonju Severance Christian Hospital in Korea from January 2010 to December 2012. RESULTS: The mean age of patients was 35.2 years old. The most frequent trauma mechanism was blunt injury (90.8%), as well as slip-and-fall down injury, motor vehicle accidents, and others. Aside from 142 early trauma deaths, a total of 4673 patients were admitted for further treatment. The most common major trauma sites of admitted patients were on the extremities (38.4%), followed by craniocerebral, abdominopelvis, and thorax. With deaths of 126 patients during in-hospital treatment, the overall mortality (142 early and 126 late deaths) was 5.6% for admitted patients. Ages > or =55, injury severity score > or =16, major craniocerebral injury, cardiopulmonary resuscitation at arrival, probability of survival <25% calculated from the trauma and injury severity score were independent predictors of trauma mortality in multivariate analysis. CONCLUSION: The epidemiology of the trauma patients studied was found to be mainly blunt trauma. This finding is similar to previous papers in terms of demographics and mechanism. Trauma patients who have risk factors of mortality require careful management in order to prevent trauma-related deaths.

Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report / 결핵및호흡기질환

Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus.

Left External Iliac and Common Femoral Artery Occlusion Following Blunt Abdominal Trauma without Associated Bone Injury

Blunt abdominal trauma may cause peripheral vascular injuries. However, blunt abdominal trauma rarely results in injuries to the external iliac and common femoral arteries, which often stem from regional bone fractures. Here, we present the case of a patient who had experienced trauma in the lower abdominal and groin area three months before presenting to the hospital, but these injuries did not involve bone fractures and had been managed conservatively. The patient came to the hospital because of left lower leg claudication that gradually became severe. Computed tomography angiography confirmed total occlusion of the external iliac and common femoral arteries. The patient underwent femorofemoral bypass grafting and was discharged uneventfully.

Complications of Central Venous Totally Implantable Access Port: Internal Jugular Versus Subclavian Access / 대한중환자의학회지

BACKGROUND: Totally implantable access port (TIAP) provides reliable, long term vascular access with minimal risk of infection and allows patients normal physical activity. With wide use of ports, new complications have been encountered. We analyzed TIAP related complications and evaluated the outcomes of two different percutaneous routes of access to superior vena cava. METHODS: All 172 patients who underwent port insertion with internal jugular approach (Group 1, n = 92) and subclavian approach (Group 2, n = 79) between August 2011 and May 2013 in a single center were analyzed, retrospectively. Medical records were analyzed to compare the outcomes and the occurrence of port related complications between two different percutaneous routes of access to superior vena cava. RESULTS: Median follow-up for TIAP was 278 days (range, 1-1868). Twenty four complications were occurred (14.0%), including pneumothorax (n = 1, 0.6%), migration/malposition (n = 4, 2.3%), pinch-off syndrome (n = 4, 2.3%), malfunction (n = 2, 1.1%), infection (n = 8, 4.7%), and venous thrombosis (n = 5, 2.9%). The overall incidence was 8.7% and 20.3% in each group (p = 0.030). Mechanical complications except infectious and thrombotic complications were more often occurred in group 2 (p = 0.033). The mechanical complication free probability is significantly higher in group 1 (p = 0.040). CONCLUSIONS: We suggest that the jugular access should be chosen in patients who need long term catheterization because of high incidence of mechanical complication, such as pinch-off syndrome.

Cardiac Rupture of the Junction of the Right Atrium and Superior Vena Cava in Blunt Thoracic Trauma / 대한중환자의학회지

Cardiac rupture following blunt thoracic trauma is rarely encountered, since it commonly causes death at the scene. With advances in critical care, blunt cardiac rupture has been successfully treated with well-organized team approach including an emergency physician, anesthesiologist, and cardiac surgeon. We encountered a patient with blunt cardiac rupture of the junction of the superior vena cava and right atrium that extended 7 cm to the right ventricular junction. The patient was successfully resuscitated after a closed thoracostomy and pericardiocentesis with fluid loading. Cardiac injury was repaired via mid-sternotomy without cardiopulmonary bypass. The patient recovered without complications and was discharged on the 7th day after surgery.

Erratum: Complications of Central Venous Totally Implantable Access Port: Internal Jugular Versus Subclavian Access / 대한중환자의학회지

We found an error in this article. The author's affiliation.

NADPH oxidase activation contributes to native low-density lipoprotein-induced proliferation of human aortic smooth muscle cells

Elevated plasma concentration of native low-density lipoprotein (nLDL) is associated with vascular smooth muscle cell (VSMC) activation and cardiovascular disease. We investigated the mechanisms of superoxide generation and its contribution to pathophysiological cell proliferation in response to nLDL stimulation. Lucigenin-induced chemiluminescence was used to measure nLDL-induced superoxide production in human aortic smooth muscle cells (hAoSMCs). Superoxide production was increased by nicotinamide adenine dinucleotide phosphate (NADPH) and decreased by NADPH oxidase inhibitors in nLDL-stimulated hAoSMC and hAoSMC homogenates, as well as in prepared membrane fractions. Extracellular signal-regulated kinase 1/2 (Erk1/2), protein kinase C-theta (PKCtheta) and protein kinase C-beta (PKCbeta) were phosphorylated and maximally activated within 3 min of nLDL stimulation. Phosphorylated Erk1/2 mitogen-activated protein kinase, PKCtheta and PKCbeta stimulated interactions between p47phox and p22phox; these interactions were prevented by MEK and PKC inhibitors (PD98059 and calphostin C, respectively). These inhibitors decreased nLDL-dependent superoxide production and blocked translocation of p47phox to the membrane, as shown by epifluorescence imaging and cellular fractionation experiments. Proliferation assays showed that a small interfering RNA against p47phox, as well as superoxide scavenger and NADPH oxidase inhibitors, blocked nLDL-induced hAoSMC proliferation. The nLDL stimulation in deendothelialized aortic rings from C57BL/6J mice increased dihydroethidine fluorescence and induced p47phox translocation that was blocked by PD98059 or calphostin C. Isolated aortic SMCs from p47phox-/- mice (mAoSMCs) did not respond to nLDL stimulation. Furthermore, NADPH oxidase 1 (Nox1) was responsible for superoxide generation and cell proliferation in nLDL-stimulated hAoSMCs. These data demonstrated that NADPH oxidase activation contributed to cell proliferation in nLDL-stimulated hAoSMCs.

Erratum: Complications of Central Venous Totally Implantable Access Port: Internal Jugular Versus Subclavian Access / 대한구급학회지

We found an error in this article. The author's affiliation.

Placental Transmogrification of the Lung

Placental transmogrification is a very rare lung disease, where the alveoli resemble the chorionic villi of placenta, and this change is a characteristic finding. A 31-year-old female patient presented with cough and dyspnea that had begun 2 weeks prior to admission. Along with giant bulla found in the left upper lung field, subsegmental consolidation was also identified in the lingular segment on plain chest radiograph and CT scan. Wedge resection was performed to remove the bulla. Pathologic examination of the resected bulla revealed destruction of the normal structures and characteristic villous and papillary changes. These changes led to a diagnosis of placental transmogrification. We made an encounter of an unusual placental transmogrification which had different image findings from other reported transmogrification cases. Thus, we report an atypical placental transmogrification case where both consolidation and giant bulla coexist.

A Case of Hereditary Hemorrhagic Telangiectasia Diagnosed through Spontaneous Hemothorax / 결핵및호흡기질환

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare autosomal dominant disease characterized by heterogenous multisystemic dysplasia of the vascular tissue. Prevalence of HHT is 1 in 5,000~8,000. HHT commonly presents with recurrent epistaxis, but may have more serious consequences if visceral vascular beds are involved. Approximately 30~50% of HHT cases also present with pulmonary arteriovenous malformation (PAVM). Spontaneous hemothorax is less common, and PAVM is one of the causes leading to hemothorax. Our case involved an 18-year-old female who had suddenly developed right chest pain. The reason for chest pain was due to right spontaneous hemothorax accompanied by PAVM in the right middle lobe. The patient was additionally diagnosed with HHT upon examination of her family history, specifically through her mother's symptom that included recurrent epistaxis and mucosal telangiectasia.

A Rare Case of Pericardial Actinomycosis / 감염과화학요법

Actinomycosis is a common chronic suppurative and granulomatous infection caused by anaerobic or microphilic bacteria primarily from the genus Actinomyces. However, Actinomyces is a rare cause of pericarditis. We experienced a rare case of pericardial actinomycosis. A previously healthy 44-year-old man presented with 3 days of fever, chest pain, and clinical signs of congestive heart failure. Chest computed tomography showed pericardial effusion, pericardial thickening, and bilateral pleural effusion. A subxiphoidpericardiotomy was performed, and a histological specimen was taken from the pericardium. A histological section of the pericardium showed an actinomycotic granule (sulfur granule). His symptoms and signs improved after administration of piperacillin/tazobactam and steroids. He was uneventfully discharged on oral amoxicillin/clavulanate. He recovered fully with no recurrence after six months of follow-up.