N121T and N121S substitutions on the SARS-CoV-2 spike protein impact on serum neutralization.

The N121 site on the spike protein of SARS-CoV-2 is associated with heme and its metabolite, biliverdin, which can affect antibody binding. Both N121T and N121S substitutions have been observed in natural conditions and in a hamster model of dual infection with SARS-CoV-2 and Influenza A virus. Serum pseudotype neutralization assays against HIV-1 particles carrying wild-type, N121T, and N121S spikes with immune mouse and human sera revealed that N121T and N121S mutations had a greater impact on serum neutralization than biliverdin treatment. Although N121T and N121S substitutions are not currently major SARS-CoV-2 variants of concern, this study could provide fundamental information to prepare for potential future mutations at the N121 site of SARS-CoV-2.

The degree of respiratory depression according to the effect-site concentration in remimazolam target-controlled infusion: A randomised controlled trial.

BACKGROUND: Remimazolam is not only associated with a lower incidence of respiratory depression than propofol but also in itself has the risk of respiratory depression. OBJECTIVE: We investigated respiratory depression following remimazolam infusion, targeting different effect-site concentrations using target-controlled infusion. DESIGN: A prospective, double-blind, randomised controlled study. SETTING: Tertiary hospital, Suwon, South Korea, from April 2022 to November 2022. PARTICIPANTS: One hundred and seven patients scheduled for general anaesthesia were randomised into three groups targeting remimazolam effect-site concentrations of 500 (RMZ-500) ( n  = 36), 1000 (RMZ-1000) ( n  = 35) and 1500 ng ml -1 (RMZ-1500) ( n  = 36). INTERVENTIONS: Remimazolam was solely infused for 10 min according to target effect-site concentrations. According to the degree of SpO 2 decrease, oxygen desaturations were managed with the following respiratory supports: jaw-thrust for SpO 2 less than 97%, 100% oxygen delivery for SpO 2 less than 93% and assisted ventilation for SpO 2 less than 90%. MAIN OUTCOME MEASURES: The incidence of each respiratory support, along with respiratory variables (at baseline, 5 min and 10 min after remimazolam infusion) and loss of consciousness were observed for 10 min after remimazolam target-controlled infusion. RESULTS: Both RMZ-1000 and RMZ-1500 required more frequent respiratory support than RMZ-500 (both P  < 0.001), with nearly identical frequencies between RMZ-1000 and RMZ-1500. In terms of respiratory support, the incidence of assisted ventilation was significantly lower in RMZ-500 (2.8%) than RMZ-1000 (48.6%) and RMZ-1500 (50%) ( P  < 0.001). RMZ-1000 and RMZ-1500 achieved loss of consciousness in all patients; RMZ-500 only achieved loss of consciousness in 86.1% of patients ( P  = 0.010). In patients who maintained spontaneous respiration, tidal volume decreased by 41 to 48% and respiratory rate increased by 118 to 158% at 5 and 10 min, significantly compared to baseline in all groups ( P  < 0.001). CONCLUSIONS: Remimazolam infusion, like that of other benzodiazepines, led to respiratory depression, which was more prominent at higher target effect-site concentrations. Therefore, appropriate countermeasures should be developed to prevent oxygen desaturation. TRIAL REGISTRATION: CRIS ( https://cris.nih.go.kr ), identifier: KCT0006952.

CSF1R-Mediated Myeloid Cell Depletion Prolongs Lifespan But Aggravates Distinct Motor Symptoms in a Model of Multiple System Atrophy.

As the CNS-resident macrophages and member of the myeloid lineage, microglia fulfill manifold functions important for brain development and homeostasis. In the context of neurodegenerative diseases, they have been implicated in degenerative and regenerative processes. The discovery of distinct activation patterns, including increased phagocytosis, indicated a damaging role of myeloid cells in multiple system atrophy (MSA), a devastating, rapidly progressing atypical parkinsonian disorder. Here, we analyzed the gene expression profile of microglia in a mouse model of MSA (MBP29-hα-syn) and identified a disease-associated expression profile and upregulation of the colony-stimulating factor 1 (Csf1). Thus, we hypothesized that CSF1 receptor-mediated depletion of myeloid cells using PLX5622 modifies the disease progression and neuropathological phenotype in this mouse model. Intriguingly, sex-balanced analysis of myeloid cell depletion in MBP29-hα-syn mice revealed a two-faced outcome comprising an improved survival rate accompanied by a delayed onset of neurological symptoms in contrast to severely impaired motor functions. Furthermore, PLX5622 reversed gene expression profiles related to myeloid cell activation but reduced gene expression associated with transsynaptic signaling and signal release. While transcriptional changes were accompanied by a reduction of dopaminergic neurons in the SNpc, striatal neuritic density was increased upon myeloid cell depletion in MBP29-hα-syn mice. Together, our findings provide insight into the complex, two-faced role of myeloid cells in the context of MSA emphasizing the importance to carefully balance the beneficial and adverse effects of CSF1R inhibition in different models of neurodegenerative disorders before its clinical translation.SIGNIFICANCE STATEMENT Myeloid cells have been implicated as detrimental in the disease pathogenesis of multiple system atrophy. However, long-term CSF1R-dependent depletion of these cells in a mouse model of multiple system atrophy demonstrates a two-faced effect involving an improved survival associated with a delayed onset of disease and reduced inflammation which was contrasted by severely impaired motor functions, synaptic signaling, and neuronal circuitries. Thus, this study unraveled a complex role of myeloid cells in multiple system atrophy, which indicates important functions beyond the previously described disease-associated, destructive phenotype and emphasized the need of further investigation to carefully and individually fine-tune immunologic processes in different neurodegenerative diseases.

Evidence for the circulation of genotype 4 Eurasian avian-like lineage swine H1N1 influenza A viruses on Korean swine farms, obtained using a newly developed one-step multiplex RT-qPCR assay.

Genotype 4 (G4) Eurasian avian-like lineage swine H1N1 influenza A viruses, which are reassortants containing sequences from the pandemic 2009 H1N1 virus lineage, triple-reassortant-lineage internal genes, and EA-lineage external genes, have been reported in China since 2013. These have been predominant in pig populations since 2016 and have exhibited pandemic potential. In this study, we developed a one-step multiplex RT-qPCR assay targeting the M, HA1, and PB2 genes to detect G4 and related EA H1N1 viruses, with detection limits of 1.5 × 101 copies/µL and 1.15 × 10-2 ng/µL for the purified PCR products and RNA templates, respectively. The specificity of the detection method was confirmed using various influenza virus subtypes. When the one-step multiplex RT-qPCR assay was applied to swine respiratory samples collected between 2020 and 2022 in Korea, a virus related to G4 EA H1N1 strains was detected. Phylogenetic analysis based on portions of all eight genome segments showed that the positive sample contained HA, NA, PB2, NS, and NP genes closely related to those of G4 EA H1N1 viruses, confirming the ability of our assay to accurately detect G4 EA H1N1 viruses in the field.

Machine learning-based prediction model for postoperative delirium in non-cardiac surgery.

BACKGROUND: Postoperative delirium is a common complication that is distressing. This study aimed to demonstrate a prediction model for delirium. METHODS: Among 203,374undergoing non-cardiac surgery between January 2011 and June 2019 at Samsung Medical Center, 2,865 (1.4%) were diagnosed with postoperative delirium. After comparing performances of machine learning algorithms, we chose variables for a prediction model based on an extreme gradient boosting algorithm. Using the top five variables, we generated a prediction model for delirium and conducted an external validation. The Kaplan-Meier and Cox survival analyses were used to analyse the difference of delirium occurrence in patients classified as a prediction model. RESULTS: The top five variables selected for the postoperative delirium prediction model were age, operation duration, physical status classification, male sex, and surgical risk. An optimal probability threshold in this model was estimated to be 0.02. The area under the receiver operating characteristic (AUROC) curve was 0.870 with a 95% confidence interval of 0.855-0.885, and the sensitivity and specificity of the model were 0.76 and 0.84, respectively. In an external validation, the AUROC was 0.867 (0.845-0.877). In the survival analysis, delirium occurred more frequently in the group of patients predicted as delirium using an internal validation dataset (p < 0.001). CONCLUSION: Based on machine learning techniques, we analyzed a prediction model of delirium in patients who underwent non-cardiac surgery. Screening for delirium based on the prediction model could improve postoperative care. The working model is provided online and is available for further verification among other populations. TRIAL REGISTRATION: KCT 0006363.

Comparison of the acid suppression effects between low-dose esomeprazole and famotidine in healthy subjects.

OBJECTIVE: Famotidine, an H2 receptor antagonist (H2RA), is mainly prescribed to alleviate the early symptoms of gastritis. Our aim was to explore the possibilities of low-dose esomeprazole as a treatment of gastritis as well as the pharmacodynamic (PD) properties of esomeprazole and famotidine. MATERIALS AND METHODS: A randomized, multiple-dose, 6-sequence, 3-period crossover study was conducted with a 7-day washout between periods. For each period, the subjects were administered one dose of esomeprazole 10 mg or famotidine 20 mg or esomeprazole 20 mg each day. To evaluate the PDs, the 24-hour gastric pH was recorded after single and multiple doses. The mean percentage of time during which the gastric pH was above 4 was evaluated for PD assessment. To confirm the pharmacokinetic (PK) characteristics of esomeprazole, blood was collected for up to 24 hours after multiple doses. RESULTS: 26 subjects completed the study. Following the multiple doses of esomeprazole 10 mg, esomeprazole 20 mg, and famotidine 20 mg, the mean percentages of time during which the gastric pH was above 4 over the course of 24 hour were 35.77 ± 19.56%, 53.75 ± 20.55%, and 24.48 ± 17.36%, respectively. After multiple doses, the time of peak plasma concentration at steady state (tmax,ss) was 1.00 and 1.25 hours for 10 and 20 mg of esomeprazole, respectively. The geometric mean ratio and its 90% confidence interval of area under the plasma drug concentration-time curve in steady state (AUCT,ss) and maximum concentration of drug in plasma in steady state (Cmax,ss) for esomeprazole 10 mg compared to 20 mg were 0.3654 (0.3381 - 0.3948) and 0.5066 (0.4601 - 0.5579), respectively. CONCLUSION: The PD parameters of esomeprazole 10 mg were comparable to those of famotidine after multiple doses. These findings provide support for further evaluating the use of 10 mg of esomeprazole as a treatment option for gastritis.

Children's learning and development in conflict- and crisis-affected countries: Building a science for action.

This paper critically reviews the opportunities and challenges in designing and conducting actionable research on the learning and development of children in conflict- and crisis-affected countries. We approached our review through two perspectives championed by Edward Zigler: (a) child development and social policy and (b) developmental psychopathology in context. The aim of the work was to answer the following questions: What works to enhance children's learning and development in such contexts? By what mechanisms? For whom? Under what conditions? How do experiences and conditions of crisis affect the basic processes of children's typical development? The review is based on a research-practice partnership started in the Democratic Republic of the Congo in 2010 and expanded to research in Niger and Lebanon in 2016. The focus of the research is on the impact of Healing Classrooms (a set of classroom practices) and Healing Classrooms Plus (an additional set of targeted social and emotional learning activities), developed by the International Rescue Committee, on children's academic outcomes and social and emotional learning. We sought to extract lessons from this decade of research for building a global developmental science for action. Special attention is paid to the importance of research-practice partnerships, conceptual frameworks, measurement and methodology. We conclude by highlighting several essential features of a global developmental science for action.

Accuracy of Continuous and Noninvasive Hemoglobin Monitoring in the Presence of CO2 Insufflation: An Observational Pilot Study.

BACKGROUND Laparoscopic surgery has several benefits, but it requires prolonged carbon dioxide (CO2) insufflation. Several factors affect the accuracy of continuous and noninvasive hemoglobin (SpHb) monitoring, but the effects of CO2 insufflation are undetermined. This study investigated the effect of CO2 insufflation on SpHb monitoring in laparoscopic surgery. MATERIAL AND METHODS Twenty patients undergoing laparoscopic gastrectomy were enrolled. Anesthesia was maintained using sevoflurane and remifentanil within an end-tidal CO2 of 30-45 mmHg. The CO2 insufflation was maintained at 12 mmHg using CO2. SpHb was monitored with a Radical-7 Pulse CO-Oximeter, and laboratory hemoglobin (tHb) was analyzed using a satellite blood analyzer. RESULTS Forty paired measurements were analyzed. The mean perfusion index, SpHb, and tHb were 3.10±1.77%, 10.92±1.48 g/dL, and 11.51±0.88 g/dL, respectively. SpHb underestimated tHb with a bias (precision) of -0.59 (1.28 g/dL), and the 95% limit of agreement was wide (-3.11 to 1.92 g/dL). SpHb was moderately correlated with tHb (r=0.50, 95% CI: 0.23 to 0.70). The concordance rate was 67%. ΔSpHb was not correlated with ΔtHb (r=0.29, 95% CI: -0.18 to -0.65). A similar bias, wider limits of agreement, a higher |SpHb-tHb|, but more significant correlation between SpHb and tHb were observed for the "PaCO2 <40 mmHg" range compared with the "40 mmHg ≤PaCO2" range. CONCLUSIONS SpHb may have an acceptable accuracy but has a weak trending ability in the presence of CO2 insufflation, and it can be affected by PaCO2. Further research on the effects of CO2 insufflation on SpHb is needed.

Comparison of remifentanil concentrations with and without dexmedetomidine for the prevention of emergence cough after nasal surgery: a randomized double-blinded trial.

BACKGROUND: Preventing emergence cough after nasal surgery is critical. Emergence cough can provoke immediate postoperative bleeding, which leads to upper airway obstruction. In the present study, we compared the effect-site concentration (Ce) of remifentanil to prevent emergence cough after propofol anesthesia for nasal surgery when remifentanil was or was not combined with dexmedetomidine. METHODS: Forty-seven patients with propofol-remifentanil anesthesia for nasal surgery were randomly assigned to a dexmedetomidine group (Group D, n = 23) or a saline group (Group S, n = 24). Group D and Group S were infused with dexmedetomidine (0.5 µg/kg) and saline, respectively, for 10 min before the completion of surgery. A predetermined Ce of remifentanil was infused until extubation. Remifentanil Ce to prevent cough in 50 and 95% of patients (EC50 and EC95) was estimated using modified Dixon's up-and-down method and isotonic regression. Hemodynamic and recovery parameters were recorded. RESULTS: The EC50 of remifentanil Ce was significantly lower in Group D than in Group S (2.15 ± 0.40 ng/mL vs. 2.66 ± 0.36 ng/mL, p = 0.023). The EC95 (95% CI) of remifentanil Ce was also significantly lower in Group D [2.75 (2.67-2.78) ng/mL] than in Group S [3.16 (3.06-3.18) ng/mL]. Emergence and recovery variables did not differ between the two groups. CONCLUSION: The remifentanil EC50 to prevent cough after propofol-remifentanil anesthesia was significantly lower (approximately 19%) when a combination of remifentanil and 0.5 µg/kg dexmedetomidine was used than when remifentanil infusion alone was used in patients undergoing nasal surgery. Therefore, the Ce of remifentanil may be adjusted to prevent emergence cough when used in combination with dexmedetomidine. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03622502 , August 9, 2018).

A comparison of the effects and usability of two exoskeletal robots with and without robotic actuation for upper extremity rehabilitation among patients with stroke: a single-blinded randomised controlled pilot study.

BACKGROUND: Robotic rehabilitation of stroke survivors with upper extremity dysfunction may yield different outcomes depending on the robot type. Considering that excessive dependence on assistive force by robotic actuators may interfere with the patient's active learning and participation, we hypothesised that the use of an active-assistive robot with robotic actuators does not lead to a more meaningful difference with respect to upper extremity rehabilitation than the use of a passive robot without robotic actuators. Accordingly, we aimed to evaluate the differences in the clinical and kinematic outcomes between active-assistive and passive robotic rehabilitation among stroke survivors. METHODS: In this single-blinded randomised controlled pilot trial, we assigned 20 stroke survivors with upper extremity dysfunction (Medical Research Council scale score, 3 or 4) to the active-assistive robotic intervention (ACT) and passive robotic intervention (PSV) groups in a 1:1 ratio and administered 20 sessions of 30-min robotic intervention (5 days/week, 4 weeks). The primary (Wolf Motor Function Test [WMFT]-score and -time: measures activity), and secondary (Fugl-Meyer Assessment [FMA] and Stroke Impact Scale [SIS] scores: measure impairment and participation, respectively; kinematic outcomes) outcome measures were determined at baseline, after 2 and 4 weeks of the intervention, and 4 weeks after the end of the intervention. Furthermore, we evaluated the usability of the robots through interviews with patients, therapists, and physiatrists. RESULTS: In both the groups, the WMFT-score and -time improved over the course of the intervention. Time had a significant effect on the WMFT-score and -time, FMA-UE, FMA-prox, and SIS-strength; group × time interaction had a significant effect on SIS-function and SIS-social participation (all, p < 0.05). The PSV group showed better improvement in participation and smoothness than the ACT group. In contrast, the ACT group exhibited better improvement in mean speed. CONCLUSIONS: There were no differences between the two groups regarding the impairment and activity domains. However, the PSV robots were more beneficial than ACT robots regarding participation and smoothness. Considering the high cost and complexity of ACT robots, PSV robots might be more suitable for rehabilitation in stroke survivors capable of voluntary movement. Trial registration The trial was registered retrospectively on 14 March 2018 at ClinicalTrials.gov (NCT03465267).

Incidence of hemi-diaphragmatic paresis after ultrasound-guided intermediate cervical plexus block: a prospective observational study.

PURPOSE: An intermediate cervical plexus block (CPB) targets the posterior cervical space between the sternocleidomastoid muscle and the prevertebral fascia. The phrenic nerve descends obliquely on the surface of the anterior scalene muscle beneath the prevertebral fascia after originating from the C3-C5 ventral rami. Therefore, the phrenic nerve can be affected by a local anesthetic during an intermediate CPB, depending on the permeability characteristics of the prevertebral fascia. This study investigated whether an intermediate CPB affects the phrenic nerve, inducing hemidiaphragmatic paresis. METHODS: In this prospective observational study, 20 patients undergoing single-incision transaxillary robot-assisted right thyroidectomy were enrolled. The intermediate CPB (0.25% ropivacaine 0.2 ml/kg) was performed at the C4-5 intervertebral level carefully, without penetrating the prevertebral fascia, before the patient emerged from general anesthesia. Diaphragmatic motions of the block side were measured by M-mode ultrasonography at three time points: before anesthesia (baseline) and at 30 and 60 min after the intermediate CPB. Hemidiaphragmatic paresis was divided into three grades, depending on the percentage of diaphragm movement compared to the baseline: none (> 75%), partial paresis (25-75%), and complete paresis (< 25%). RESULTS: No patient showed any partial or complete ipsilateral hemidiaphragmatic paresis within 60 min after the intermediate CPB. CONCLUSION: Intermediate CPB using 0.2 ml/kg of 0.25% ropivacaine at the C4-5 intervertebral level did not cause ipsilateral hemidiaphragmatic paresis. This may imply that the effect of the intermediate CPB on the phrenic nerve is not significant.

Obstructive sleep apnea as a risk factor for incident end stage renal disease: a nationwide population-based cohort study from Korea.

BACKGROUND: Obstructive sleep apnea (OSA) is known to be associated with metabolic dysregulation and incident cardiovascular diseases. However, its association with end-stage renal disease (ESRD) has not been clarified. This study aimed to evaluate longitudinally whether OSA is an independent risk factor for ESRD. METHODS: This retrospective nationwide population-based cohort study included data on 67,359 patients with OSA and 336,795 age-, sex- and years of the enrollment-matched controls without OSA obtained from the Korean National Health Insurance Service database from 2009 to 2014. The study population was followed up from baseline to the date of ESRD diagnosis or until 2016. A Cox proportional-hazards model with multivariable adjustment was used to evaluate the association between OSA and incident ESRD. RESULTS: A significantly higher incident ESRD risk (adjusted hazard ratio: 1.29, 95% confidence interval 1.02-1.62) was observed for patients older than 40 years with OSA than for matched controls, when adjusted for age, sex, income status, smoking, alcohol consumption, body mass index, diabetes, hypertension, dyslipidemia, estimated glomerular filtration rate, and proteinuria. The OSA group remained predictive of higher risk of ESRD incidence in subgroups of age ≥ 65 years, female sex, hypertension, dyslipidemia, proteinuria, and chronic kidney disease. CONCLUSION: OSA was associated with a higher risk of incident ESRD. Understanding the association between OSA and ESRD might provide further insights to establish national health care policy.

Correction: Clinical efficacy of upper limb robotic therapy in people with tetraplegia: a pilot randomized controlled trial.

In the original version of the article the authors incorrectly stated that: "One case study provided evidence of some improvements in motor performance and spasticity [19], while several other studies only provided evidence on the feasibility of UER as an assessment tool; however, the fact that the manufacturer funded these studies lessens their objectivity [15, 20-24]." This is not correct as the manufacturers did not fund the studies. The correct phrase therefore should have read: "One case study provided evidence of some improvements in motor performance and spasticity [19], while several other studies provided evidence focusing more on the feasibility of UER rather than the clinical efficacy [15, 20-24]." The authors would like to apologise for this error.This has been corrected in both the PDF and HTML versions of the Article.

Clinical efficacy of upper limb robotic therapy in people with tetraplegia: a pilot randomized controlled trial.

STUDY DESIGN: A pilot randomized controlled trial. OBJECTIVES: To evaluate the clinical efficacy of upper limb robotic therapy in people with tetraplegia. SETTING: Inpatient rehabilitation hospital in Seoul, Korea. METHODS: Participants were randomly allocated to a robotic therapy (RT) or occupational therapy (OT) group. Both groups received usual care plus 30 min of additional therapy per day for 4 weeks. The additional therapy provided to the OT group was OT, and the additional therapy provided to RT group was RT using the Armeo Power. Primary outcomes were the Medical Research Council scale of each key muscle and Upper Extremity Motor Score (UEMS) for the trained arm. Secondary outcomes were the Spinal Cord Independence Measurement version III (SCIM-III) subscale and total score. Evaluations were performed at baseline and 4 weeks. RESULTS: A total of 34 individuals with tetraplegia were included; 17 in each group. At 4 weeks, the median (IQR) change in UEMS in the RT group was 1/25 (0 to 3) points compared with 0/25 (-1 to 1) points in the OT group (p = 0.03). The median (IQR) change in total SCIM-III score in the RT group was 7/100 (1.5 to 11) points compared with 0/100 (-8 to 4) points in the OT group (p < 0.01). CONCLUSIONS: There were small improvements in motor strength and SCIM-III scores in the RT group, but there were no statistically significant differences between the groups. Further studies are required for a better understanding of the effects of RT for people with tetraplegia.

Robot-assisted gait training for balance and lower extremity function in patients with infratentorial stroke: a single-blinded randomized controlled trial.

BACKGROUND: Balance impairments are common in patients with infratentorial stroke. Although robot-assisted gait training (RAGT) exerts positive effects on balance among patients with stroke, it remains unclear whether such training is superior to conventional physical therapy (CPT). Therefore, we aimed to investigate the effects of RAGT combined with CPT and compared them with the effects of CPT only on balance and lower extremity function among survivors of infratentorial stroke. METHODS: This study was a single-blinded, randomized controlled trial with a crossover design conducted at a single rehabilitation hospital. Patients (n = 19; 16 men, three women; mean age: 47.4 ± 11.6 years) with infratentorial stroke were randomly allocated to either group A (4 weeks of RAGT+CPT, followed by 4 weeks of CPT+CPT) or group B (4 weeks of CPT+CPT followed by 4 weeks of RAGT+CPT). Changes in dynamic and static balance as indicated by Berg Balance Scale scores were regarded as the primary outcome measure. Outcome measures were evaluated for each participant at baseline and after each 4-week intervention period. RESULTS: No significant differences in outcome-related variables were observed between group A and B at baseline. In addition, no significant time-by-group interactions were observed for any variables, indicating that intervention order had no effect on lower extremity function or balance. Significantly greater improvements in secondary functional outcomes such as lower extremity Fugl-Meyer assessment (FMA-LE) and scale for the assessment and rating of ataxia (SARA) were observed following the RAGT+CPT intervention than following the CPT+CPT intervention. CONCLUSION: RAGT produces clinically significant improvements in balance and lower extremity function in individuals with infratentorial stroke. Thus, RAGT may be useful for patients with balance impairments secondary to other pathologies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02680691. Registered 09 February 2016; retrospectively registered.

Shallow nasal RAE tube depth after head and neck surgery: association with preoperative and intraoperative factors.

PURPOSE: To evaluate risk factors associated with improper postoperative nasal Ring-Adair-Elwyn (RAE) tube depth. METHODS: We retrospectively enrolled 133 adult patients who were admitted to the intensive care unit (ICU) with the nasal RAE tube after head and neck surgery. Postoperative chest radiography was performed to confirm nasal RAE tube depth immediately after the patient was admitted to the ICU. Proper tube depth was defined as the tube tip between 2 and 7 cm above the carina. The patients were divided into the proper-depth group (78 patients) and the improper-depth group (55 patients). Patients' characteristics were collected. The risk factors for improper postoperative tube depth were assessed using logistic regression analysis. MAIN RESULTS: All patients who showed improper tube depth had a shallow tube depth (the tube tip > 7 cm above the carina). Multivariable analysis revealed that tall stature [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.08-1.25; P < 0.001], prolonged anesthesia duration (OR 1.16; 95% CI 1.02-1.32; P = 0.026), and right-sided surgical field as compared to the left (OR 0.36; 95% CI 0.14-0.93; P = 0.034) or median field (OR 0.25; 95% CI 0.07-0.85; P = 0.027) were risk factors associated with postoperative shallow tube depth. CONCLUSIONS: Tall stature, prolonged anesthesia duration, and right-sided surgical field were independent risk factors for postoperative shallow nasal RAE tube depth.

Increased expression of the Cbl family of E3 ubiquitin ligases decreases Interleukin-2 production in a rat model of peripheral neuropathy.

BACKGROUND: Interleukin 2 (IL-2) influences the development and severity of pain due to its antinociceptive and immunomodulatory effects. Its production is influenced by the increased expression of c-Cbl (Casitas B-lineage lymphoma proto-oncogene) and Cbl-b E3 ubiquitin ligases. We evaluated the effects on IL-2-mediated changes in c-Cbl and Cbl-b expression in a rat model of chronic neuropathic pain. METHODS: Peripheral neuropathy was induced in adult male Sprague-Dawley rats weighing 250-300 g by chronic spinal nerve ligation. Half of the spinal cord ipsilateral to the nerve injury was harvested at 1, 3, and 6 weeks, and the expression levels of IL-2, c-Cbl, Cbl-b, phospholipase C-γ1 (PLC-γ1), ZAP70, and protein kinase Cθ (PKCθ), as well as ubiquitin conjugation, were evaluated. RESULTS: Total IL-2 mRNA levels were significantly decreased at 3 and 6 weeks after nerve injury compared to those in sham-operated rats. The mRNA levels of c-Cbl and Cbl-b, as well as the level of ubiquitin conjugation, were significantly increased at 3 and 6 weeks. In contrast, the levels of phosphorylated ZAP70 and PLC-γ1 were decreased at 3 and 6 weeks after spinal nerve ligation. Ubiquitination of PLC-γ1 and PKCθ was increased at 3 and 6 weeks. CONCLUSIONS: Our results suggest that ubiquitin and the E3 ubiquitin ligases c-Cbl and Cbl-b function as neuroimmune modulators in the subacute phase of neuropathic pain after nerve injury.

Safety and Efficacy of Tolvaptan in Korean Patients with Hyponatremia Caused by the Syndrome of Inappropriate Antidiuretic Hormone.

BACKGROUND: The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). METHODS: Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4. RESULTS: Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = -0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775-0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500-0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected. CONCLUSION: TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV.

Tumor necrosis factor α-converting enzyme inhibitor attenuates lipopolysaccharide-induced reactive oxygen species and mitogen-activated protein kinase expression in human renal proximal tubule epithelial cells.

Tumor necrosis factor-α (TNFα) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which TNFα-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS (10 µg/ml) in the presence or absence of a type 1 TACE inhibitor (1 µM) or type 2 TACE inhibitor (10 µM). LPS treatment induced increased serum creatinine, TNFα, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.

Association of serum adiponectin level with albuminuria in chronic kidney disease patients.

BACKGROUND: Adiponectin, a peptide hormone secreted from adipocytes, exerts anti-diabetic, anti-atherogenic, and anti-inflammatory properties. We aimed to determine the relationship between serum adiponectin levels and albuminuria, and evaluate determinant factors for serum adiponectin in patients with chronic kidney disease (CKD). METHODS: In total, 1442 CKD patients were included and divided into three groups according to their albumin-to-creatinine ratios: patients with normoalbuminuria (N = 228), microalbuminuria (N = 444), and macroalbuminuria (N = 761). Serum adiponectin was specifically assayed with a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Serum adiponectin was significantly higher in patients with macroalbuminuria than in those without macroalbuminuria (9.7 ± 6.0, 12.4 ± 9.0, and 14.9 ± 11.0 µg/mL in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). Univariate linear regression analysis showed that the serum adiponectin concentrations were correlated with age, the albumin-to-creatinine ratio, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, whereas they were negatively correlated with body mass index, the estimated glomerular filtration rate, and serum albumin and triglyceride levels. The stepwise regression multiple analysis showed that sex; the estimated glomerular filtration rate; body mass index; total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; and logarithm of the albumin-to-creatinine ratio were independently associated with the logarithm of serum adiponectin levels (r = 0.55, p < 0.001). CONCLUSION: Serum adiponectin concentrations are higher in patients with increasing albuminuria, and these levels are associated with renal insufficiency and lipid profiles.