Recurrence-free survival after curative resection of non-small cell lung cancer between inhalational gas anesthesia and propofol-based total intravenous anesthesia: a multicenter, randomized, clinical trial (GAS TIVA trial): protocol description.

BACKGROUND: Surgery is the primary treatment for non-small cell lung cancer (NSCLC), but microscopic residual disease may be unavoidable. Preclinical studies have shown that volatile anesthetics might suppress host immunity and promote a pro-malignant environment that supports cancer cell proliferation, migration, and angiogenesis, whereas propofol may preserve cell-mediated immunity and inhibit tumor angiogenesis. However, clinical evidence that propofol-based total intravenous anesthesia (TIVA) can reduce tumor recurrence after curative resection remains inconsistent due to the retrospective observational nature of previous studies. Therefore, we will test the hypothesis that the recurrence-free survival (RFS) after curative resection of NSCLC is higher in patients who received TIVA than volatile anesthetics (GAS) in this multicenter randomized trial. METHODS: This double-blind, randomized trial will enroll patients at 22 international sites, subject to study registration, institutional review board approval, and patient written informed consent. Eligible patients are adult patients undergoing lung resection surgery with curative intent for NSCLC. Exclusion criteria will be contraindications to study drugs, American Society of Anesthesiologists physical status IV or higher, or preexisting distant metastasis or malignant tumor in other organs. At each study site, enrolled subjects will be randomly allocated into the TIVA and GAS groups with a 1:1 ratio. This pragmatic trial does not standardize any aspect of patient care. However, potential confounders will be balanced between the study arms. The primary outcome will be RFS. Secondary outcomes will be overall survival and complications within postoperative 7 days. Enrollment of 5384 patients will provide 80% power to detect a 3% treatment effect (hazard ratio of 0.83) at alpha 0.05 for RFS at 3 years. DISCUSSION: Confirmation of the study hypothesis would demonstrate that a relatively minor and low-cost alteration in anesthetic management has the potential to reduce cancer recurrence risk in NSCLC, an ultimately fatal complication. Rejection of the hypothesis would end the ongoing debate about the relationship between cancer recurrence and anesthetic management. TRIAL REGISTRATION: The study protocol was prospectively registered at the Clinical trials ( https://clinicaltrials.gov , NCT06330038, principal investigator: Hyun Joo Ahn; date of first public release: March 25, 2024) before the recruitment of the first participant.

Closed reduction and internal fixation for tillaux fractures, based on pre-operative three-dimensional computed tomography.

OBJECTIVE: This study aimed to propose treatment protocol and identify patterns of tillaux fractures using three-dimensional (3D) computed tomography (CT) analysis and to describe an effective reduction technique. METHODS: Forty-two juvenile patients with tillaux fractures were evaluated with 3D-CT scan for fracture displacement pattern and received surgical treatment. Tillaux fragment was reduced by pushing the superomedial quadrant part of the fragment slightly downward towards the ankle joint from anterolateral to posteromedial through 5-mm skin incisions with mosquito forceps. A 4.0 cannulated screw was subsequently inserted from the anterolateral to the posteromedial side parallel to the ankle joint. We analysed the distance and direction of fracture displacement with 3D-CT before the surgery. Pre-operative and post-operative plain radiographs were evaluated. RESULTS: Pre-operative 3D-CT analysis revealed a common fracture pattern, varus tilt, and external rotation of fragment. We achieved satisfactory reduction with residual fracture gaps less than 2 mm in 42 cases. Two cases had a 13-mm anterior gap that was reduced by mini-open reduction because of periosteal impingement. No significant clinical complications were found. CONCLUSION: The closed reduction technique developed based on the fracture pattern identified by 3D-CT anatomical analysis is safe and effective in treating tillaux fractures.

Analgesic effectiveness of continuous versus single-injection adductor canal block in addition to continuous popliteal sciatic nerve block for bimalleolar and trimalleolar ankle fracture surgery: Prospective randomized controlled trial.

BACKGROUND: The adductor canal block is a well-known procedure for controlling postoperative pain after medial malleolus fracture surgery. Continuous nerve block is a viable option for blocking pain for a longer period although the literature on this subject is scarce. Therefore, this study aimed to compare continuous adductor canal block (cACB) group to single-injection adductor canal block (sACB) group in those with bimalleolar or trimalleolar ankle fractures. The procedure was performed in addition to a continuous sciatic nerve block for postoperative pain relief and patient satisfaction. METHODS: The study included 57 patients who had bimalleolar or trimalleolar ankle fractures and underwent open reduction and internal fixation between August 2016 and June 2018. Each patient received a continuous sciatic nerve block and was divided into two groups: those who received cACB and those who received sACB. Each postoperative pain was scored at 4, 8, 12, 24, 48, and 72 h after surgery. Additionally, the consumption of rescue medications and patient satisfaction were evaluated. RESULTS: The two groups displayed no disparity in medial side ankle pain at 4 h and 8 h after surgery, but significantly higher pain in the sACB group at 12, 24, 48, and 72 h after surgery. However, there was no difference in the pain at the lateral side of ankle and consumption of rescue medication. In addition, the cACB group showed more satisfaction than the sACB group did. CONCLUSION: CACB is better than sACB in terms of postoperative pain control and patient satisfaction. cACB can be used for postoperative pain control in ankle fractures involving the medial malleolus. LEVEL OF EVIDENCE: Prospective Randomized Controlled Trial, Level 2.

Suprapatellar intramedullary nail combined with screw fixation has comparable surgical outcomes to minimally invasive locking plate fixation in ipsilateral tibial plateau and shaft fractures.

PURPOSE: To compare union rate, union time, alignment, and complication rate in ipsilateral tibia plateau and shaft fractures treated via suprapatellar intramedullary nailing with screw fixation and minimally invasive locking plate fixation. MATERIALS AND METHODS: A retrospective study was conducted on 48 patients who underwent minimally invasive plate fixation (n = 35) or suprapatellar intramedullary nailing with screw fixation (n = 13), for the treatment of ipsilateral tibial plateau and shaft fractures with at least 1-year follow-up. Union rate, union time, radiologic alignment, and complication rate such as malalignment, nonunion, and fracture-related infection (FRI) were investigated. RESULTS: Demographic data were not different between the two groups. Coronal plane alignment was 0.17 ± 4.23 in the plate group and -0.48 ± 4.17 in the intramedullary nail group (p = 0.637). Sagittal plane alignment was -0.13 ± 5.20 in the plate group and -1.50 ± 4.01 in the suprapatellar intramedullary nail group (p = 0.313). Coronal and sagittal malalignment recorded equal results: (p > 0.99), FRI (p = 0.602), nonunion and union times recorded (p = 0.656) and (p = 0.683, 0.829), respectively, and showed no significant difference between the two groups. CONCLUSION: Suprapatellar intramedullary nailing with screw fixation had similar surgical outcomes with minimally invasive locking plate fixation in ipsilateral tibial plateau and shaft fractures in terms of union rate, union time, alignment, and complication rate. Thus, frequent use of intramedullary nailing combined with screw fixation is anticipated in patients with ipsilateral tibial plateau and shaft fractures when the soft tissue condition is not desirable. LEVEL OF EVIDENCE: Level III.

Pediatric Spinal Trauma at a Single Level 1 Trauma Center: Review of 62 Cases.

Background: Traumatic spinal injuries in children are uncommon and result in different patterns of injuries due to the anatomical characteristics of children's spines. However, there are only a few epidemiological studies of traumatic spinal injury in children. The purpose of this study was to investigate the characteristics of traumatic spinal injury in children. Methods: We retrospectively reviewed the cases of pediatric patients (age < 18 years) with traumatic spinal injury who were treated at a level 1 trauma center between January 2017 and December 2021. We divided them into three groups according to age and analyzed demographics, injury mechanism, level of injury, and injury pattern. Results: A total of 62 patients (255 fractures) were included, and the mean age was 13.8 ± 3.2 years. There were 5 patients (22 fractures) in group I (0-9 years), 24 patients (82 fractures) in group II (10-14 years), and 33 patients (151 fractures) in group III (15-17 years). Both the Injury Severity Score and the Revised Trauma Score were highest in group I, but there was no statistical difference between the age groups. Fall from height was the most common injury mechanism, of which 63% were suicide attempts. The level of spinal injury was different in each age group, T10-L2 injury being the most common. In all age groups, the number of multilevel continuous injury was larger than that of single-level injury or multilevel noncontinuous injury. Surgical intervention was required in 33.9%, and mortality was 3.2%. Conclusions: In our study, fall from height was the most common mechanism of injury, and there were many suicide attempts associated with mental health issues. Thoracolumbar junction injuries were predominant, and the rate of multilevel contiguous injuries was high. The support and interest of the society and families for adolescent children seem crucial in preventing spinal trauma, and image testing of the entire spine is essential when evaluating pediatric spinal injuries.

Intraoperative assessment of hindfoot alignment using C-arm fluoroscopy.

BACKGROUND: Hindfoot malalignment can cause various foot and ankle problems. For better surgical performance and correction of hindfoot malalignments, reliable intraoperative determination of hindfoot alignment is essential. However, there is no standard method for the intraoperative assessment of hindfoot alignment. We devised an intraoperative modified Méary posteroanterior (IOPPA) view to assess intraoperative hindfoot alignment. This study aimed to compare this intraoperative method with other radiographic hindfoot alignment measurements. METHODS: Thirty-seven patients (47 feet) with various foot and ankle conditions scheduled to undergo surgery were prospectively recruited. Before surgery, the Saltzman, long axial, and modified Méary views were taken in a controlled and standardized fashion. IOPPA views were obtained under simulated weight bearing conditions using C-arm fluoroscopy in the operating room before surgery. The relationship between the IOPPA view and the three radiographic hindfoot alignments was evaluated using Pearson's correlation. RESULTS: The mean hindfoot alignment angle was varus 3.50° (CI, varus 1.91 to 5.08) on the Saltzman view, varus 2.00° (CI, varus 0.60 to 3.39) on the long axial view, varus 0.13° (CI, valgus 1.41 to varus 1.67) on the modified Méary view, and varus 1.32° (CI, valgus 0.02 to varus 2.65) on IOPPA view. The IOPPA view and the three other hindfoot alignment views were found to be significantly correlated (r = 0.60 for the Saltzman view, r = 0.50 for the long axial view, r = 0.71 for the modified Méary view, P < .05). The intraobserver ICC (Intraclass Correlation Coefficient) value was 0.974 and interobserver ICC (Intraclass Correlation Coefficient) value was 0.988 for the IOPPA view (P < .001). CONCLUSION: There was a statistically significant correlation between the IOPPA view and the other three hindfoot alignment views. We also found that interobserver and intraobserver ICC values were excellent. This study proposes that the IOPPA view can be used as a reliable intraoperative assessment tool for hindfoot alignment. LEVEL OF EVIDENCE: Prospective study.

Comparison of suprapatellar intramedullary nailing versus minimal invasive locked plating for proximal tibia fractures.

PURPOSE: To compare the radiological alignment, union time, union rate, and complication rate between suprapatellar intramedullary nails and minimally invasive locking plate fixation in the treatment of proximal tibial fractures. MATERIALS AND METHODS: We retrospectively analyzed 103 patients who underwent plate fixation (n = 50) or suprapatellar intramedullary nailing (n = 53) for proximal tibial fractures involving the meta-diaphyseal junction between November 2015 and October 2020 at our institution. The union rate, union time, radiologic alignments, and complications, such as malalignment, nonunion, and deep infection, were investigated. RESULTS: The demographic data did not differ between the plate and suprapatellar intramedullary nail groups. The alignment of the coronal plane was 0.24 ± 3.19 in the plate group and - 0.49 ± 2.22 in the intramedullary nail group (p = 0.196). Sagittal plane alignment was - 0.29 ± 4.97 in the plate group and 0.24 ± 4.12 in the intramedullary nail group (p = 0.571), and coronal malalignment (p = 0.196), sagittal malalignment (p = 0.57), deep infection (p = 0.264), nonunion (p = 0.695), union time (p = 0.329), and final union rate (p = 0.699) were not significantly different between groups. CONCLUSION: Compared with the minimally invasive locking compression plate group, the suprapatellar intramedullary nail group yielded comparable results in terms of radiological alignment and complications. Considering that proximal tibial fractures are associated with high-energy trauma and severe soft tissue damage, we believe that a suprapatellar intramedullary nail may be a good alternative. LEVEL OF EVIDENCE: Level III.

Hemodynamic responses to 1 MAC desflurane inhalation during anesthesia induction with propofol bolus and remifentanil continuous infusion: a prospective randomized single-blind clinical investigation.

BACKGROUND: Desflurane is not recommended during anesthesia induction because of its sympathetic stimulation effect, particularly in patients with myocardial ischemic disease. To date, the hemodynamic response to 1 MAC desflurane inhalation in combination with remifentanil infusion during anesthesia induction has rarely been reported. METHODS: This investigation was designed to compare hemodynamic responses to 1 MAC desflurane (group D, n = 200) with sevoflurane (group S, n = 200) during anesthesia induction and endotracheal intubation in adult patients undergoing elective spine surgery. Subgroup analysis of the different age subgroups was also performed. With continuous infusion of remifentanil 0.1 µg/kg/min, anesthesia was induced with propofol bolus, and endotracheal intubation was performed after muscle relaxation. Heart rate (HR) and mean arterial blood pressure (MAP) were measured every minute for 5 min after anesthesia induction (T1-5) and after endotracheal intubation (T6-10). RESULTS: HR was significantly higher in group D (n = 182) than in group S (n = 173) at T3-10 except at T6 (1 min after intubation) (all P < 0.05). In the age-based subgroup analyses, which subdivided the group D and S into four subgroups based on patient's age, the changes in HR from baseline values were significantly different between the coeval subgroups of patients in their 20-29 years and 30-39 years of age (all P < 0.05). MAP was reduced from baseline value, irrespective of group and age. CONCLUSION: Inhalation of 1 MAC desflurane during anesthesia induction with propofol bolus and remifentanil continuous infusion and during endotracheal intubation was more likely to induce elevations in HR more likely than 1 MAC sevoflurane, especially in younger patients. TRIAL REGISTRATION: This study was registered in the Clinical Research Information Service (CRIS, http://cris.nih.go.kr ) of the Republic of Korea on Feb 12, 2016 (Registration No. KCT 0,001,813).

Assessment of Perioperative Atelectasis Using Lung Ultrasonography in Patients Undergoing Pneumoperitoneum Surgery in the Trendelenburg Position: Aspects of Differences according to Ventilatory Mode.

BACKGROUND: During robotic gynecologic pneumoperitoneum surgery in the Trendelenburg position, aeration loss leads to perioperative atelectasis. Recently developed ventilator mode pressure-controlled ventilation volume-guaranteed (PCV-VG) mode could provide adequate ventilation with lower inspiratory pressure compared to volume-controlled ventilation (VCV); we hypothesized that PCV-VG mode may be beneficial in reducing perioperative atelectasis via low tidal volume (VT) of 6 mL/kg ventilation during robotic gynecologic pneumoperitoneum surgery in the Trendelenburg position. We applied lung ultrasound score (LUS) for detecting perioperative atelectasis. We aimed to compare perioperative atelectasis between VCV and PCV-VG with a low VT of 6 mL/kg during pneumoperitoneum surgery in the Trendelenburg position using LUS. METHODS: Patients scheduled for robotic gynecologic surgery were randomly allocated to the VCV (n = 41) or PCV-VG group (n = 41). LUS, ventilatory, and hemodynamic parameters were evaluated at T1 (before induction), T2 (10 minutes after induction in the supine position), T3 (10 minutes after desufflation of CO2 in the supine position), and T4 (30 minutes after emergence from anesthesia in the recovery room). RESULTS: Eighty patients (40 with PCV-VG and 40 with VCV) were included. Demographic data showed no significant differences between the groups. The total LUS has changed from baseline to T4, 0.63 (95% confidence interval [CI], 0.32, 0.94) to 1.77 (95% CI, 1.42, 2.21) in the VCV group and 0.86 (95% CI, 0.56, 1.16) to 1.43 (95% CI, 1.08, 1.78) in the PCV-VG group (P = 0.170). In both groups, total LUS increased significantly compared to the baseline values. CONCLUSION: Using a low VT of 6 mL/kg during pneumoperitoneum surgery in the Trendelenburg position, our study showed no evidence that PCV-VG ventilation was superior to VCV in terms of perioperative atelectasis. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0006404.

Perineural dexamethasone reduces rebound pain after ropivacaine single injection interscalene block for arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: A single injection interscalene block (ISB) is a common regional analgesic technique in patients undergoing arthroscopic shoulder surgery. However, rebound pain after ISB resolution may reduce its overall benefit. Our primary aim was to assess whether perineural dexamethasone reduces the intensity and incidence of rebound pain in patients undergoing arthroscopic shoulder surgery under general anesthesia combined with a preoperative single injection ISB. METHODS: The patients were randomly assigned to receive single injection ISB using either 0.5% ropivacaine (control) or 0.5% ropivacaine containing 5 mg of dexamethasone. The primary outcomes were the pain score difference before and after ISB resolution, and the incidence of rebound pain. The secondary outcomes were the onset and duration of rebound pain, the presence of sleep disturbances due to postoperative pain, the first time when an analgesic was requested, and pain scores at various predefined time points. RESULTS: Pain increase following ISB resolution was lower in the dexamethasone group compared with the control group (4.5±2.4 and 6.9±2.2, respectively, p<0.001). The incidence of rebound pain was significantly lower in the dexamethasone group compared with the control group (37.1% and 82.9%, respectively, p<0.001). The controls experienced greater sleep disturbance during the postoperative period compared with those who received ISB with perineural dexamethasone. CONCLUSIONS: Perineural dexamethasone added to ISB using ropivacaine led to a much smoother resolution of ISB, reflected in a significantly smaller increase in pain after block resolution, a lower incidence of rebound pain and a lower sleep disturbance during the first postoperative week. TRIAL REGISTRATION NUMBER: Clinical Trial Registry of Korea (KCT0004418).

Probing drug delivery and mechanisms of action in 3D spheroid cells by quantitative analysis.

Human tumor cells in a 3-dimensional (3D) spheroid can reflect the characteristics of solid tumors by forming cell-cell interactions and microenvironments. This makes 3D cell culture useful for preclinical stability and drug efficacy tests. In this study, the drug delivery and action mechanisms in SK-N-SH neuroblastoma cells cultured in 3D spheroids were quantitatively compared to those cultured in 2D monolayers using confocal microscopy imaging and inductively coupled plasma-mass spectrometry. In the 3D spheroids, cisplatin only accessed the surface, accumulating in the cells on the spheroid exterior. As a result, an increased cellular amount of cisplatin was required to obtain similar cytotoxicity in the 3D spheroid cells to that in 2D monolayers. The mechanisms of reduction of drug efficacy by dimethyl sulfoxide (DMSO) in the 3D spheroid cells compared to those in the 2D monolayer cells were further investigated. DMSO reduced the drug cytotoxicity by forming stable DMSO-substituted compounds that inhibited the cellular uptake of cisplatin and DNA-Pt adduct formation. The quantitative analysis used in this study is promising for understanding drug delivery and drug action mechanisms in cells in various microenvironments.

The effect of anesthetic agents on cerebral vasospasms after subarachnoid hemorrhage: A retrospective study.

Cerebral vasospasm is the most important cause of morbidity after an aneurysm clipping in the early postoperative period. The aim of this retrospective study was to evaluate whether the incidence of vasospasms differs when using propofol or desflurane for an emergent aneurysm clipping.The data from 102 patients (50 in the propofol group, 52 in the desflurane group) were analyzed. The occurrence of vasospasm based on daily transcranial Doppler, angiography, and cerebral infarction during 14 days after surgery were compared by anesthetic agents. Postoperative data including Glasgow Coma Scale (GCS) score on day 14 after surgery, and the Glasgow Outcome Scale (GOS) score at 3 months were documented.Patients that intraoperatively received propofol for anesthesia maintenance, had higher incidence of transcranial Doppler (TCD)-evident vasospasm than those that received desflurane (54% vs 30.8%, P = .027). The occurrence of TCD-evident vasospasm was still higher (odds ratio: 2.84; 95% confidence interval: 1.12-7.20) in the propofol group than in the desflurane group after adjusting for confounding factors. However, the incidence of angiographic vasospasm, cerebral infarction, and interventions to treat cerebral vasospasms were similar between both groups. GCS score on day 14 after surgery and the GOS score at 3 months were similar between groups.No effect of anesthetic agents on angiographic vasospasm, cerebral infarction, or clinical outcome was observed, whereas desflurane anesthesia was associated with a lower incidence of TCD-evident vasospasms compared to propofol anesthesia. Our study provides a basis for further randomized controlled studies in a larger patient population to clarify the effects of anesthetic agents on the occurrence of cerebral vasospasms.

Effects of Tranexamic Acid Based on its Population Pharmacokinetics in Pediatric Patients Undergoing Distraction Osteogenesis for Craniosynostosis: Rotational Thromboelastometry (ROTEMTM) Analysis.

Background: Distraction osteogenesis for craniosynostosis is associated with significant hemorrhage. Additionally, patients usually require several transfusions. Tranexamic acid (TXA) is effective for reducing blood loss and the need for transfusions during surgeries. However, the significance of TXA infusion has not been thoroughly described yet. Methods: Forty-eight children undergoing distraction osteogenesis for craniosynostosis were administered intraoperative TXA infusion (loading dose of 10 mg/kg for 15 min, followed by continuous infusion at 5 mg/kg/h throughout surgery; n = 23) or normal saline (control, n = 25). Rotational thromboelastometry (ROTEMTM) was conducted to monitor changes in coagulation perioperatively. Results: Blood loss during surgery was significantly lower in the TXA-treated group than it was in the control group (81 vs. 116 mL/kg, P = 0.003). Furthermore, significantly fewer transfusions of red blood cells and fresh frozen plasma were required in the TXA group. In the control group, clotting time during the postoperative period was longer than it was during the preoperative period. Similarly, clot strength was weaker during the postoperative period. D-dimer levels dramatically increased in the control group compared with the TXA group after surgery. The duration of mechanical ventilation and the number of postoperative respiratory-related complications were significantly greater in the control group than they were in the TXA group. Conclusions: TXA infusion based on population pharmacokinetic analysis is effective in reducing blood loss and the need for transfusions during the surgical treatment of craniosynostosis. It can also prevent the increase in D-dimer levels without affecting systemic hemostasis.

Structural characterization of small molecular ions by ion mobility mass spectrometry in nitrogen drift gas: improving the accuracy of trajectory method calculations.

The investigation of ion structures based on a combination of ion mobility mass spectrometry (IM-MS) experiments and theoretical collision cross section (CCS) calculations has become important to many fields of research. However, the accuracy of current CCS calculations for ions in nitrogen drift gas limits the information content of many experiments. In particular, few studies have evaluated and attempted to improve the theoretical tools for CCS calculation in nitrogen drift gas. In this study, based on high-quality experimental measurements and theoretical modeling, a comprehensive evaluation of various aspects of CCS calculations in nitrogen drift gas is performed. It is shown that the modification of the ion-nitrogen van der Waals (vdW) interaction potential enables accurate CCS predictions of 29 small ions with ca. 3% maximum relative error. The present method exhibits no apparent systematic bias with respect to ion CCS (size) and dipole moment, suggesting that the method adequately describes the long-range interactions between the ions and the buffer gas. However, the method shows limitations in reproducing experimental CCS at low temperatures (<150 K) and for macromolecular ions, and calculations for these cases should be complemented by CCS calculation methods in helium drift gas. This study presents an accurate and well-characterized CCS calculation method for ions in nitrogen drift gas that is expected to become an important tool for ion structural characterization and molecular identification. The experimental values reported here also provide a foundation for future studies aiming at developing more efficient computational tools.

Reference Intervals of Thromboelastometric Evaluation of Coagulation in Pediatric Patients with Congenital Heart Diseases: A Retrospective Investigation.

BACKGROUND Rotational thromboelastometry (ROTEM®) is a point-of-care test for coagulation, enabling physicians to make a swift decision. The aim of this investigation was to establish reference intervals of thromboelastometric evaluation for coagulation in pediatric patients with congenital heart diseases (CHD). MATERIAL AND METHODS As baseline data, 3 assays of ROTEM® (INTEM, EXTEM, and FIBTEM) were measured after anesthesia induction. ROTEM® parameters were clotting time (CT), amplitude at 10 min (A10), clot formation time (CFT), a angle, maximal clot firmness (MCF), clot lysis index at 60 min (LI60), and maximal clot elasticity (MCE). As age is a well-known factor for maturation, age groups were determined as follows; 1) <1 month, 2) 1-3 months, 3) 4-12 months, 4) 1-3 years, 5) 4-6 years, 6) 7-12 years, and 7) 13-16 years. Reference limits representing 95% of distribution of ROTEM® parameters and 90% confidence intervals of upper and lower reference limits were calculated. RESULTS The data of 413 patients were analyzed. Although INTEM CT was prolonged, significantly shorter CT and CFT, steeper α, and greater A10, MCF, and MCE were shown in patients age <3 months compared to older children. CONCLUSIONS Reference intervals of thromboelastometric evaluation for coagulation from pediatric patients with CHD were shown to have similar pattern to those obtained from healthy pediatric patients. Pediatric patients with CHD, even with cyanosis, were demonstrated to have functionally intact coagulation profile before surgery.

Structure and assembly mechanisms of toxic human islet amyloid polypeptide oligomers associated with copper.

Amyloidosis is a clinical disorder implicated with the formation of toxic amyloid aggregates. Despite their pathological significance, it is challenging to define the structural characteristics of amyloid oligomers owing to their metastable nature. Herein, we report structural and mechanistic investigations of human islet amyloid polypeptide (hIAPP) oligomers, found in type II diabetes mellitus, in both the absence and presence of disease-relevant metal ions [i.e., Cu(ii) and Zn(ii)]. These metal ions show suppressive effects on hIAPP fibrillation and facilitate the generation of toxic oligomers. Using circular dichroism spectroscopy, transmission electron microscopy, gel electrophoresis, small-angle X-ray scattering, and ion mobility-mass spectrometry, we investigated the assembly mechanisms of hIAPP oligomers in the presence and absence of metal ions. Oligomerization of both metal-free hIAPP and metal-associated hIAPP monomers is initiated following a similar growth model. However, in the presence of Cu(ii), hIAPP monomers self-assemble into small globular aggregates (Rg ∼ 45 Å) with a random coil structure. This Cu(ii)-associated hIAPP oligomer shows an off-pathway aggregation, and is suggested to be an end product which is toxic to pancreatic ß-cells. On the other hand, metal-free hIAPP and Zn(ii)-associated hIAPP monomers generate relatively less toxic aggregates that eventually grow into fibrils. We suggest that the coordination of hIAPP to Cu(ii) and the relatively high stability (Ka, ca. 108 M-1) of hIAPP-Cu(ii) complexes result in the abnormal conformation and toxicity of hIAPP oligomers. Overall, through combining multiple biophysical methods, our studies suggest that molecular interactions between hIAPP and Cu(ii) induce a different pathway for hIAPP assembly. This work will advance our knowledge of the conformational basis, assembly mechanism, and toxicity of small soluble amyloid oligomers.

Blood lead concentration and related factors in Korea from the 2008 National Survey for Environmental Pollutants in the Human Body.

This study evaluated blood lead concentrations in the Korean general population and the correlation between various exposure sources using data from the 2008 Korea National Survey for Environmental Pollutants in the Human Body (National Institute of Environmental Research, Korea). The general and occupational characteristics were gathered from 5136 participants who were 20 years of age and older using a structured questionnaire. Blood lead concentrations were analyzed using an atomic absorption spectrophotometer. Statistical analysis was performed using multiple linear regressions of the log lead concentrations to the independent variables such as age, gender, smoke, herbal medication and drug consumption, drinking water, and living area. Geometric mean (GM) blood lead concentrations in Korean adults were 19.7 µg/l. The blood lead concentrations increased with age; the highest concentrations were found in the 50-69-year age group (p<0.001). Males were higher than in females (p<0.001). Current smokers and drinkers had higher concentrations than nonsmokers (p<0.001) and nondrinkers (p<0.001), respectively. People who took herbal medication and drug consumption were higher than those who did not (p<0.001). Education level was negatively associated with blood lead concentration (p<0.001). People living in or around industrial areas had elevated blood lead concentration (p<0.001). Family income was also negatively associated with lead concentration, but not significantly. For drinking water, the underground water (spring or well water) drinking group had higher concentrations than other types of water drinking groups, but not significantly (p=0.063). The blood lead concentrations by occupation were significant (p<0.034): the highest was in laborer and Agricultural-Fishery-Forestry and the lowest in office workers. In women, blood lead concentrations tended to decrease with increasing delivery times, but not significantly. The blood lead concentration (GM) of the general adult population in Korea has decreased over time from 45.8 µg/l (1999) to 19.7 µg/l (2008). Although it is still higher than in other countries such as the United States and Canada, it is rapidly decreasing. Gender, age, smoking and alcohol drinking status, herbal medication and drug consumption, education level, living area and occupation were significantly related to the blood lead concentrations in Korea.

Supramolecular inhibition of amyloid fibrillation by cucurbit[7]uril.

Amyloid fibrils are insoluble protein aggregates comprised of highly ordered ß-sheet structures and they are involved in the pathology of amyloidoses, such as Alzheimer's disease. A supramolecular strategy is presented for inhibiting amyloid fibrillation by using cucurbit[7]uril (CB[7]). CB[7] prevents the fibrillation of insulin and ß-amyloid by capturing phenylalanine (Phe) residues, which are crucial to the hydrophobic interactions formed during amyloid fibrillation. These results suggest that the Phe-specific binding of CB[7] can modulate the intermolecular interaction of amyloid proteins and prevent the transition from monomeric to multimeric states. CB[7] thus has potential for the development of a therapeutic strategy for amyloidosis.

Host-guest chemistry in the gas phase: complex formation of cucurbit[6]uril with proton-bound water dimer.

The hydration of cucurbit[6]uril (CB[6]) in the gas phase is investigated using electrospray ionization traveling wave ion mobility mass spectrometry (ESI-TWIM-MS). Highly abundant dihydrated and tetrahydrated species of diprotonated CB[6] are found in the ESI-TWIM-MS spectrum. The hydration patterns of the CB[6] ion and the dissociation patterns of the hydrated CB[6] ion indicate that two water molecules are bound to each other, forming a water dimer in the CB[6] complex. Ion mobility studies combined with the structures calculated by density functional theory suggest that the proton-bound water dimer is present as a Zundel-like structure in the CB[6] portal, forming a hydrogen bond network with carbonyl groups of the CB[6]. When a large guest molecule is bound to a CB[6] portal, water molecules cannot bind to the portal. In addition, the strong binding energy of the water dimer blocks the portal, hindering the insertion of the long alkyl chain of the guest molecule into the CB[6] cavity. With small alkali metal cations, such as Li(+) and Na(+), a single water molecule interacts with the CB[6] portal, forming hydrogen bonds with the carbonyl groups of CB[6]. A highly stable Zundel-like structure of the proton-bound water dimer or a metal-bound water molecule at the CB[6] portal is suggested as an initial hydration process for CB[6], which is only dissolved in aqueous solution with acid or alkali metal ions.