HMGB1 Is a Prognostic Factor for Mortality in Acute Kidney Injury Requiring Renal Replacement Therapy.

INSTRUCTION: High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine that reportedly causes kidney injury and other organ damage in rodent acute kidney injury (AKI) models. However, it remains unclear whether HMGB1 is associated with clinical AKI and related outcomes. This study aimed to evaluate the association with HMGB1 and prognosis of AKI requiring continuous renal replacement therapy (CRRT). METHODS: AKI patients treated with CRRT in our intensive care unit were enrolled consecutively during 2013-2016. Plasma HMGB1 was measured on initiation. Classic initiation was defined as presenting at least one of the following conventional indications: hyperkalemia (K ≥6.5 mEq/L), severe acidosis (pH <7.15), uremia (UN >100 mg/dL), and diuretics-resistant pulmonary edema. Early initiation was defined as presenting no conventional indications. The primary outcome was defined as 90-day mortality. RESULTS: A total of 177 AKI patients were enrolled in this study. HMGB1 was significantly associated with the primary outcome (hazard ratio, 1.06; 95% CI, 1.04-1.08). When the patients were divided into two-by-two groups by the timing of CRRT initiation and the HMBG1 cutoff value obtained by receiver operating curve (ROC) analysis, the high HMGB1 group (>10 ng/mL) with classic initiation was significantly associated with the primary outcome compared with the others, even after adjusting for other factors including the nonrenal serial organ failure assessment (SOFA) score. CONCLUSION: HMGB1 was associated with 90-day mortality in AKI patients requiring CRRT. Notably, the highest mortality was observed in the high HMGB1 group with classic initiation. These findings suggest that CRRT should be considered for AKI patients with high HMGB1, regardless of the conventional indications.

Different Roles of Functional and Structural Renal Markers Measured at Discontinuation of Renal Replacement Therapy for Acute Kidney Injury.

INTRODUCTION: Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) has been associated with an unacceptably high mortality of 50% or more. Successful discontinuation of RRT is thought to be linked to better outcomes. Although functional and structural renal markers have been evaluated in AKI, little is known about their roles in predicting outcomes at the time of RRT discontinuation. METHODS: In this prospective single-center cohort study, we analyzed patients who received continuous RRT (CRRT) for AKI between August 2016 and March 2018 in the intensive care unit of the University of Tokyo Hospital (Tokyo, Japan). Clinical parameters and urine samples were obtained at CRRT discontinuation. Successful CRRT discontinuation was defined as neither resuming CRRT for 48 h nor receiving intermittent hemodialysis for 7 days from the CRRT termination. Major adverse kidney events (MAKEs) were defined as death, requirement for dialysis, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline at day 90. RESULTS: Of 73 patients, who received CRRT for AKI, 59 successfully discontinued CRRT and 14 could not. Kinetic eGFR, urine volume, urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary L-type fatty acid binding protein were predictive for CRRT discontinuation. Of these factors, urine volume had the highest area under the curve (AUC) 0.91 with 95% confidence interval [0.80-0.96] for successful CRRT discontinuation. For predicting MAKEs at day 90, the urinary NGAL showed the highest AUC 0.76 [0.62-0.86], whereas kinetic eGFR and urine volume failed to show statistical significance (AUC 0.49 [0.35-0.63] and AUC 0.59 [0.44-0.73], respectively). CONCLUSIONS: Our prospective study confirmed that urine volume, a functional renal marker, predicted successful discontinuation of RRT and that urinary NGAL, a structural renal marker, predicted long-term renal outcomes. These observations suggest that the functional and structural renal makers play different roles in predicting the outcomes of severe AKI requiring RRT.

Urinary chloride concentration as a prognostic marker in critically ill patients.

AIM: Associations have been reported among serum chloride concentration, mortality and incidence of acute kidney injury (AKI) in intensive care units (ICU). This study aimed to examine associations among urinary chloride, mortality, and AKI incidence in ICU patients. METHODS: A retrospective observational study was conducted among medical-surgical ICU in a tertiary hospital wherein 170 consecutive ICU patients were evaluated from October 2015 to March 2016 and 116 patients were enrolled. Serial data of serum and urine electrolytes from day 1 to day 4 of ICU admission were examined. The primary and secondary outcomes were ICU mortality and incidence of AKI in the ICU, respectively. RESULTS: Among the 116 enrolled patients, 15 (13%) died during their ICU stay. Although serum and urinary sodium and potassium on day 1 did not significantly differ between ICU survivors and non-survivors, urinary chloride concentration on day 1 was significantly lower in non-survivors. Receiver operating characteristic analysis showed that the cutoff value of day 1 urinary chloride concentration for prediction of ICU mortality was 53 mEq/L. The lower urinary chloride concentration group on day 1 showed a significantly lower survival rate, even in long-term follow-up, compared with the higher urinary chloride group. Addition of day 1 urinary chloride concentration improved prediction of AKI incidence in the ICU by Sequential Organ Failure Assessment score alone. CONCLUSION: Lower urinary chloride concentration was associated with increased mortality and incidence of AKI in the ICU. Further investigation is necessary to clarify the mechanism of urinary chloride regulation.

Fluorescence characterization of heavily Eu3+-doped lanthanum gallate glass spheres with high quenching concentration.

Highly Eu2O3-doped (up to 30 mol%) La2O3-Ga2O3 glasses were synthesized by an aerodynamic levitation technique. The red emission associated with D05 level of Eu3+was most intense at 20 mol% Eu2O3, indicating a small effect of concentration quenching even at high Eu concentration. The fluorescence decay curves indicated that the dominant transition mechanism at high Eu concentration was fast energy migration among the Eu3+ ions, which averaged the environment of the Eu, yielding a nearly single-exponential decay of D05→F27 emission. Lifetime of the D05 level gradually decreased with Eu2O3 over the 5-25 mol% and rapidly decreased at 30 mol%, very consistent with the observed emission spectra.

Kinetic estimated glomerular filtration rate as a predictor of successful continuous renal replacement therapy discontinuation.

AIM: No standardized criteria for continuous renal replacement therapy (CRRT) discontinuation have been established. Kinetic estimated glomerular filtration rate (eGFR) is a newly developed estimation method based on dynamic changes of serum creatinine expected to reflect the true GFR. This study aimed to evaluate the predictive role of kinetic eGFR for CRRT discontinuation. METHODS: A retrospective single-centre cohort study was conducted. Acute kidney injury (AKI) patients who received CRRT between May 2015 and April 2016 were enrolled. Successful CRRT discontinuation was defined as neither resuming CRRT for the next 48 h nor receiving intermittent haemodialysis 7 days from the CRRT discontinuation. Clinical factors associated with CRRT discontinuation were evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 52 AKI patients treated with CRRT, 38 could discontinue CRRT while 14 could not. Urine volume, regular and kinetic eGFR of days 0 (day of CRRT discontinuation) and 1 were all good predictive parameters (area under the ROC curve (AUC) > 0.7). Kinetic eGFR of day 1 showed the AUC of 0.87 [95% confidence interval 0.73-0.94]). Combining kinetic eGFR of day 1 and urine volume of day 0 gave a high AUC of 0.93 [95% confidence interval 0.82-0.97]. The combination was significantly greater than urine volume of day 0 (P = 0.008). CONCLUSION: Kinetic eGFR combined with urine volume was a better predictor for CRRT discontinuation. Evaluation of kinetic eGFR utility in other clinical settings will be necessary.

Shape of an obstacle affects the mediolateral trajectory of the lower limb during the crossing process.

In previous studies involving obstacle crossing, vertical foot clearance has been used as an indicator of the risk of contact. Under normal circumstances, individuals do not always cross over obstacles with the same height on both sides, and depending on the shape of the obstacle, the risk of contact may differ depending on the foot elevation position. Therefore, we investigated whether task-related control of the mediolateral foot position is adapted to the shape of the obstacle. Sixteen healthy young adults performed a task in which they crossed over two obstacles with different shapes while walking: a trapezoidal obstacle and a rectangular obstacle, as viewed from the frontal plane. It was shown that when crossing over a trapezoidal obstacle, the participants maintained foot clearance by controlling the mediolateral direction, which chose the height that needed to be cleared. The results of this study suggest that the lower limb movements that occur during obstacle crossing are controlled not only in the vertical direction but also in the mediolateral direction by adjusting the foot trajectory to reduce the risk of contact. It was demonstrated that control was not only based on the height of the obstacle directly under the foot but also in the foot mediolateral direction, considering the shape of the entire obstacle, including the opposite limb.

Dynamic stability during level walking and obstacle crossing in children aged 2-5 years estimated by marker-less motion capture.

In the present study, dynamic stability during level walking and obstacle crossing in typically developing children aged 2-5 years (n = 13) and healthy young adults (n = 19) was investigated. The participants were asked to walk along unobstructed and obstructed walkways. The height of the obstacle was set at 10% of the leg length. Gait motion was captured by three RGB cameras. 2D body landmarks were estimated using OpenPose, a marker-less motion capture algorithm, and converted to 3D using direct linear transformation (DLT). Dynamic stability was evaluated using the margin of stability (MoS) in the forward and lateral directions. All the participants successfully crossed the obstacles. Younger children crossed the obstacle more carefully to avoid falls, as evidenced by obviously decreased gait speed just before the obstacle in 2-year-olds and the increased in maximum toe height with younger age. There was no significant difference in the MoS at the instant of heel contact between children and adults during level walking and obstacle crossing in the forward direction, although children increased the step length of the lead leg to a greater extent than the adults to ensure base of support (BoS)-center of mass (CoM) distance. In the lateral direction, children exhibited a greater MoS than adults during level walking [children: 9.5%, adults: 6.5%, median, W = 39.000, p < .001, rank-biserial correlation = -0.684]; however, some children exhibited a smaller MoS during obstacle crossing [lead leg: -5.9% to 3.6% (min-max) for 4 children, 4.7%-6.4% [95% confidence interval (CI)] for adults, p < 0.05; trail leg: 0.1%-4.4% (min-max) for 4 children, 4.7%-6.4% (95% CI) for adults, p < 0.05]]. These results indicate that in early childhood, locomotor adjustment needed to avoid contact with obstacles can be observed, whereas lateral dynamic stability is frangible.

Solute Clearance Evaluation and Filter Clotting Prediction in Continuous Renal Replacement Therapy.

Unexpected filter clotting is a major problem in continuous renal replacement therapy (CRRT). Reduced solute clearance is observed prior to filter clotting. This single-center, retrospective, observational study aimed to determine whether reduced solute clearance of low- and medium-molecular-weight molecules in CRRT can predict filter clotting. Solute clearances of urea and myoglobin (Mb) were measured at 24 h after initiation of continuous hemodiafiltration (CHDF). Clearance per flow (CL/F) was calculated. The primary outcome was clotting of the filter in the subsequent 24 h, and 775 CHDF treatments conducted on 230 patients for at least 24 consecutive hours in our ICU were analyzed. Filter clotting was observed in 127 treatments involving 39 patients. Urea and Mb CL/F at 24 h were significantly lower in the patients who experienced clotting. Further analysis was limited to the first CHDF treatment of each patient to adjust for confounding factors. Multivariate logistic regression analysis revealed that both urea CL/F < 94% and Mb CL/F < 64% were significant predictors of clotting within the next 24 h. Lower urea and Mb CL/F measured at 24 h after CRRT initiation were associated with filter clotting in the next 24 h. Further study is necessary to ascertain whether measurement of urea and MB CL/F will help with avoiding unexpected filter clotting.

Use of the Azure Kinect to measure foot clearance during obstacle crossing: A validation study.

Obstacle crossing is typical adaptive locomotion known to be related to the risk of falls. Previous conventional studies have used elaborate and costly optical motion capture systems, which not only represent a considerable expense but also require participants to visit a laboratory. To overcome these shortcomings, we aimed to develop a practical and inexpensive solution for measuring obstacle-crossing behavior by using the Microsoft Azure Kinect, one of the most promising markerless motion capture systems. We validated the Azure Kinect as a tool to measure foot clearance and compared its performance to that of an optical motion capture system (Qualisys). We also determined the effect of the Kinect sensor placement on measurement performance. Sixteen healthy young men crossed obstacles of different heights (50, 150, and 250 mm). Kinect sensors were placed in front of and beside the obstacle as well as diagonally between those positions. As indices of measurement quality, we counted the number of measurement failures and calculated the systematic and random errors between the foot clearance measured by the Kinect and Qualisys. We also calculated the Pearson correlation coefficients between the Kinect and Qualisys measurements. The number of measurement failures and the systematic and random error were minimized when the Kinect was placed diagonally in front of the obstacle on the same side as the trail limb. The high correlation coefficient (r > 0.890) observed between the Kinect and Qualisys measurements suggest that the Azure Kinect has excellent potential for measuring foot clearance during obstacle-crossing tasks.

Bandgap control using strained beam structures for Si photonic devices.

We have demonstrated that bandgap energy of Si can be controlled by micro-mechanically structured Si beams (250 nm thick, 3 µm wide, and 15 µm long) elastically deformed by an external force. Microscopic photoluminescence spectroscopy reveals that downward bending of the beam by 3 µm reveals a red shift in the peak from ~1100 nm up to ~1300 nm. It is found from calculations based on deformation potentials and finite element method that tensile strain as large as ~1.5% is generated in the top surface of the deformed beam and responsible for the red shift of the peak. The presented result should be a proof of concept to cancel wavelength fluctuation unavoidably occurring on uncooled LSIs in terms of stress application, and thereby an enabler of wavelength division multiplexing implementation on a chip. The applications of other beam materials such as Ge and GaAs are discussed.

Acute Kidney Injury in Sepsis: Evidence From Asia.

Acute kidney injury (AKI) is one of the most frequent complications of sepsis. Because sepsis and AKI synergistically worsen the outcomes of critically ill patients, better therapeutics against septic AKI urgently are required. In addition to the complexity of disease mechanisms of both sepsis and AKI, there is substantial regional variation in clinical practice, which further hampers the development of new treatments for septic AKI. To overcome this problem, evidence accumulation is necessary for building the foundation for developing novel septic AKI treatments. This review provides a summary of updated evidence regarding septic AKI from Asian regions.

Different Biomarker Kinetics in Critically Ill Patients with High Lactate Levels.

We evaluated the association of the kinetics of interleukin-6 (IL-6), neutrophil gelatinase-associated lipocalin (NGAL), and high-mobility group box 1 (HMGB1) with intensive care unit (ICU) mortality in critically ill patients with hyperlactatemia. This proof-of-concept study was conducted with prospectively enrolled patients admitted to a medical/surgical ICU with hyperlactatemia (lactate levels >4 mmol/L). Blood lactate, IL-6, NGAL, and HMGB1 were measured every 2 h until 6 h post ICU admission. The primary outcome was ICU mortality. Of thirty patients in this study, 14 patients (47%) had sepsis, and the ICU mortality was 47%. IL-6 and NGAL levels were significantly higher in septic patients than in non-septic patients. On kinetic analysis, the lactate levels were significantly decreased in survivors, and the NGAL levels were significantly increased in non-survivors. Among septic patients, a decline in IL-6 levels were observed in survivors. The HMGB1 levels were unchanged in survivors and non-survivors regardless of sepsis complication. Non-septic patients with higher reduction rate of lactate and HMGB1 had the lowest mortality than the others. ICU patients exhibited different kinetic patterns in lactate, NGAL, and IL-6, but HMGB1 did not seem to change over the 6-h duration. Further studies are necessary to evaluate the efficacy of the combination of the inflammatory biomarkers with lactate.

Principal Vibration Modes of the La2O3-Ga2O3 Binary Glass Originated from Diverse Coordination Environments of Oxygen Atoms.

La2O3-Ga2O3 binary glass exhibits unusual optical properties owing to its high oxygen polarizability and low vibration energy. These optical properties include high refractive indices and a wide transmittance range. In this study, we performed classical molecular dynamics simulations on La2O3-Ga2O3 glass synthesized by an aerodynamic levitation technique. We have obtained structural models that reproduce experimental results, such as NMR, high-energy X-ray diffraction, and neutron diffraction. Based on our analysis, the structural features were clarified: 5-, 6-coordinated Ga, edge-sharing GaOx-GaOx polyhedral linkages, and oxygen triclusters. Additionally, the vibrational density of states was calculated by diagonalization of the dynamical matrix derived from the structural models and the results were compared with Raman scattering spectra. The mode analysis of the Raman spectra revealed that the principal bands at 650 cm-1 were mainly attributed to the stretching modes of the bridging and nonbridging oxygens. Meanwhile, the shoulder bands at the highest frequency of 750 cm-1 were mainly attributed to the stretching modes of the bridging oxygens and oxygen triclusters. The structural models obtained in this study well describe the characteristic local structures and vibrational properties of the La2O3-Ga2O3 glass.

Endogenous Erythropoietin and Hepatic Dysfunction in Acute Kidney Injury Requiring Renal Replacement Therapy.

Backgrounds/Objectives: Elevated erythropoietin (EPO) is observed in human acute kidney injury (AKI). Whether blood EPO level is associated with mortality or other organ dysfunction in critically ill patients is unknown. METHODS: A prospective observational cohort study of 162 AKI patients requiring renal replacement therapy (RRT) was conducted in our intensive care unit (ICU) during October 2013 through October 2016. We evaluated the relation with plasma EPO at RRT initiation and 90-day mortality, hemoglobin, urine output, and sequential organ failure assessment (SOFA) score until day 7 or discharge from the ICU. RESULTS: The analysis revealed that EPO was significantly associated with 90-day mortality with an adjusted hazard ratio of 2.13 (95% CI 1.11-5.78). Hemoglobin levels, RRT dependence, and daily urine output on days 1 through 7 did not differ between the high EPO group (≥56.2 mIU/mL) and low EPO groups (< 56.2 mIU/mL). As for organ dysfunction, hyperbilirubinemia patients (≥2.0 mg/dL; hepatic SOFA ≥2) were more frequent in the high EPO group (62.1 vs. 37.9%; p < 0.05), while other SOFA scores did not differ between both groups. Exacerbation of hepatic dysfunction was observed more frequently in the high EPO than the low EPO group (49.3 vs. 27.2%; p < 0.05). CONCLUSION: Elevated EPO was not associated with anemia or RRT dependence. However, higher rates of mortality and hepatic dysfunction were observed in high EPO patients than in low EPO patients.

Response to different furosemide doses predicts AKI progression in ICU patients with elevated plasma NGAL levels.

BACKGROUND: Furosemide responsiveness (FR) is determined by urine output after furosemide administration and has recently been evaluated as a furosemide stress test (FST) for predicting severe acute kidney injury (AKI) progression. Although a standardized furosemide dose is required for FST, variable dosing is typically employed based on illness severity, including renal dysfunction in the clinical setting. This study aimed to evaluate whether FR with different furosemide doses can predict AKI progression. We further evaluated the combination of an AKI biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), and FR for predicting AKI progression. RESULTS: We retrospectively analyzed 95 patients who were treated with bolus furosemide in our medical-surgical intensive care unit. Patients who had already developed AKI stage 3 were excluded. A total of 18 patients developed AKI stage 3 within 1 week. Receiver operating curve analysis revealed that the area under the curve (AUC) values of FR and plasma NGAL were 0.87 (0.73-0.94) and 0.80 (0.67-0.88) for AKI progression, respectively. When plasma NGAL level was < 142 ng/mL, only one patient developed stage 3 AKI, indicating that plasma NGAL measurements were sufficient to predict AKI progression. We further evaluated the performance of FR in 51 patients with plasma NGAL levels > 142 ng/mL. FR was associated with AUC of 0.84 (0.67-0.94) for AKI progression in this population with high NGAL levels. CONCLUSIONS: Although different variable doses of furosemide were administered, FR revealed favorable efficacy for predicting AKI progression even in patients with high plasma NGAL levels. This suggests that a combination of FR and biomarkers can stratify the risk of AKI progression in a clinical setting.

Low phonon energies and wideband optical windows of La2O3-Ga2O3 glasses prepared using an aerodynamic levitation technique.

xLa2O3-(100 - x)Ga2O3 binary glasses were synthesized by an aerodynamic levitation technique. The glass-forming region was found to be 20 ≤ x ≤ 57. The refractive indices were greater than 1.92 and increased linearly with increasing x. The polarizabilities of oxide ions were estimated to be 2.16-2.41 Å3, indicating that the glasses were highly ionic. The glasses were transparent over a very wide range from the ultraviolet to the mid-infrared region. The widest transparent window among the oxide glasses was from 270 nm to 10 µm at x = 55. From the Raman scattering spectra, a decrease in bridging oxide ions and an increase in non-bridging oxide ions were confirmed to occur with increasing La2O3 content. The maximum phonon energy was found to be approximately 650 cm-1, being one of the lowest among oxide glasses. These results show that La2O3-Ga2O3 binary glasses should be promising host materials for optical applications such as lenses, windows, and filters over a very wide wavelength range.

Calcium channel blocker attenuated opioid withdrawal syndrome.

Case: A 61-year-old woman was diagnosed with deep cervical abscess and enlarged mediastinal abscess. These required a protracted period of mechanical ventilation and neck and thoracic drainage surgery with daily wound lavage, necessitating the administration of large amounts of fentanyl and dexmedetomidine. After extubation, fentanyl was discontinued but dexmedetomidine was continued, and she developed hypertension, tachycardia, tachypnea, and hyperthermia within several hours; therefore, she was diagnosed with opioid withdrawal syndrome. Her symptoms failed to improve with either an increased dexmedetomidine dose or a diltiazem infusion for symptomatic management. Ultimately, 20 mg nifedipine was given through a nasogastric tube, which led to a resolution of withdrawal symptoms. Outcome: This is the first case of calcium channel blockers attenuating opioid withdrawal syndrome symptoms in a human. Conclusion: Calcium channel blockers might be alternative therapy to refractory opioid withdrawal syndrome. Case accumulation in the future is expected.