Naoki Yahagi

Diffusion tensor imaging studies of mild traumatic brain injury: a meta-analysis

Objectives To assess the possibility that diffusion tensor imaging (DTI) can detect white matter damage in mild traumatic brain injury (mTBI) patients via systematic review and meta-analysis. Methods DTI studies that compared mTBI patients and controls were searched using MEDLINE, Web of Science, and EMBASE, (1980 through April 2012). Results A comprehensive literature search identified 28 DTI studies, of which 13 independent DTI studies of mTBI patients were eligible for the meta-analysis. Random effect model demonstrated significant fractional anisotropy (FA) reduction in the corpus callosum (CC) (p=0.023, 95% CIs −0.466 to −0.035, 280 mTBIs and 244 controls) with no publication bias and minimum heterogeneity, and a significant increase in mean diffusivity (MD) (p=0.015, 95% CIs 0.062 to 0.581, 154 mTBIs and 100 controls). Meta-analyses of the subregions of the CC demonstrated in the splenium FA was significantly reduced (p=0.025, 95% CIs −0.689 to −0.046) and MD was significantly increased (p=0.013, 95% CIs 0.113 to 0.950). FA was marginally reduced in the midbody (p=0.099, 95% CIs −0.404 to 0.034), and no significant change in FA (p=0.421, 95% CIs −0.537 to 0.224) and MD (p=0.264, 95% CIs −0.120 to 0.438) in the genu of the CC. Conclusions Our meta-analysis revealed the posterior part of the CC was more vulnerable to mTBI compared with the anterior part, and suggested the potential utility of DTI to detect white matter damage in the CC of mTBI patients.

Evaluation of new acute kidney injury biomarkers in a mixed intensive care unit.

Objective:Biomarkers for detection of acute kidney injury and prediction of mortality will be useful to improve the outcomes of critically ill patients. Although several promising acute kidney injury biomarkers have been reported, evaluation in heterogeneous disease-oriented populations is necessary to confirm their reliability before their translation to clinical use. This study was undertaken to evaluate the reliability of new acute kidney injury biomarkers including urinary L-type fatty acid-binding protein with heterogeneous intensive care unit populations. Design:Prospective observational cohort study. Setting:Single-center study, 15-bed medical–surgical mixed intensive care unit at a university hospital. Patients:Three hundred thirty-nine adult critically ill patients who had been admitted to the intensive care unit were studied prospectively. Interventions:None. Measurements and Main Results:Five urinary biomarkers (L-type fatty acid-binding protein, neutrophil gelatinase-associated lipocalin, interleukin-18, N-acetyl-&bgr;-D-glucosaminidase, and albumin) were measured at intensive care unit admission. By the RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) criteria, 131 patients (39%) were diagnosed as acute kidney injury. Urinary L-type fatty acid-binding protein detected acute kidney injury better than the other biomarkers did (the area under the receiver operating characteristic curves for L-type fatty acid-binding protein 0.75, neutrophil gelatinase-associated lipocalin 0.70, interleukin-18 0.69, N-acetyl-&bgr;-D-glucosaminidase 0.62, albumin 0.69). Urinary L-type fatty acid-binding protein predicted later-onset acute kidney injury after intensive care unit admission with the highest area under the receiver operating characteristic curve value of 0.70. Furthermore, L-type fatty acid-binding protein, neutrophil gelatinase-associated lipocalin, and interleukin-18 were able to predict 14-day mortality with higher area under the receiver operating characteristic curves than acute kidney injury detection (area under the receiver operating characteristic curve for L-type fatty acid-binding protein 0.90, neutrophil gelatinase-associated lipocalin 0.83, interleukin-18 0.83). The combination of L-type fatty acid-binding protein and neutrophil gelatinase-associated lipocalin improved mortality prediction (area under the receiver operating characteristic curve 0.93). Conclusion:This prospective observational study with a cohort of heterogeneous patients treated in a mixed intensive care unit revealed that new acute kidney injury biomarkers have a significantly and moderately predictive use for acute kidney injury diagnosis and that urinary L-type fatty acid-binding protein and neutrophil gelatinase-associated lipocalin can serve as new biomarkers of mortality prediction in critical care.

Blood Volume measurement at the bedside using ICG pulse spectrophotometry.

Background In the treatment of critically ill patients, blood volume (BV) measurement requires injection of some tracer substance and subsequent blood sampling to analyze the tracer concentration. To obviate both the sampling and laboratory analysis, techniques of pulse oximetry have been adapted to the noninvasive optical measurement in the patients nose or finger of the arterial concentration of an injectable dye. Methods The authors report the clinical accuracy of a new noninvasive bedside BV measurement test that uses pulse spectrophotometry (the pulse method). The device detects pulsatile changes of tissue optical density of a nostril or a finger spanned by a probe emitting two infrared wavelengths (805 and 890 nm). After a peripheral or central intravenous injection of indocyanine green, the arterial dye concentration is continuously computed by reference to the previously measured blood hemoglobin concentration. Three types of tests of its accuracy are described here. Results In 10 healthy volunteers, the authors compared BV determined by the pulse method with an131 I‐labeled human serum albumin method. Three subject data sets were excluded because of motion artifact, a low signal:noise ratio, or both. For the other seven volunteers, the bias +/− SD of pulse spectrophotometric BV values were 0.20 +/− 0.24 1 (or 4.2 +/− 4.9%) for the nose probe and 0.34 +/− 0.31 1 (or 7.3 +/− 6.9%) for the finger probe, with a mean BV of 5 l. In 30 patients who underwent cardiac surgery, the pulse method was compared with a standard indocyanine green method using intermittent blood sampling. In three patients, the BV could not be determined by the pulse method because of motion artifact, low signal:noise ratio, or both. In 27 patients, the bias +/− SD of the BV by the pulse method was ‐0.23 +/− 0.37 l (‐5.3 +/− 8.7%) for the nose and ‐0.25 +/− 0.5 l (‐4.2 +/− 8.4%) for the finger. Patient BV ranged from 2.51 to 7.13 l (mean, 4.48 l). In 10 additional patients before cardiac surgery, BV was measured by the pulse method before and shortly after removal of 400 ml blood. The pulse method recorded a decrease of BV of 480 +/− 114 ml. Three days after venesection, the mean BV was 117 +/− 159 ml less than the predonation control. Conclusions In most patients, the pulse method provides bedside measurement of BV without blood sampling (except for hemoglobin determination), with an estimated error less than 10%. In 10‐30% of tests the method failed because of motion distortion of the record during the 10‐min data collection period or because of insufficient pulse amplitude in the test tissue.

Autotriggering caused by cardiogenic oscillation during flow-triggered mechanical ventilation.

Objectives: We noticed that in some patients after cardiac surgery, when flow triggering was used, cardiogenic oscillation might be autotriggering the ventilatory support. In a prospective study, we evaluated the degree of cardiogenic oscillation and the frequency rate of autotriggering. We suspected that autotriggering caused by cardiogenic oscillation was more common than clinically appreciated. Design: Prospective, nonrandomized, clinical study. Setting: Surgical intensive care unit in a national heart institute. Patients: A total of 104 adult patients were enrolled after cardiac surgery. Interventions: During the study period, patients were paralyzed and ventilated with intermittent mandatory ventilation at a rate of 10 breaths/min, pressure support of 10 cm H2O, and flow triggering with a sensitivity of 1 L/min. Measurements and Main Results: Because the patients would not be able to breathe spontaneously, we counted pressure‐support (PS) breaths as instances of autotriggering. Then, we classified the patients into two groups according to the number of PS breaths: an “AT group” (PS breaths of >5/min) and a “non‐AT group” (PS breaths of ≤5/min). If autotriggering occurred, we decreased the sensitivity so autotriggering disappeared (threshold triggering sensitivity). The intensity of cardiogenic oscillation was assessed as the flow and airway pressure at the airway opening. A total of 23 patients (22%) demonstrated more than five autotriggered breaths/min. During mechanical ventilation, the inspiratory flow fluctuation caused by cardiogenic oscillation was significantly greater in the AT group than in the non‐AT group (4.67 ± 1.26 L/min vs. 2.03 ± 0.86 L/min; p < .01). The AT group also showed larger cardiac output, higher ventricular filling pressures, larger heart size, and lower respiratory system resistance than the non‐AT group. As the inspiratory flow fluctuation caused by cardiogenic oscillation increased, the level of triggering sensitivity also was increased to avoid autotriggering. In the AT group with 1 L/min of sensitivity, the respiratory rate increased (19.9 ± 2.7 vs. 10 ± 0 breaths/min, p < .01), PaCO2 decreased (30.8 ± 4.0 torr [4.11 ± 0.36 kPa] vs. 37.6 ± 4.3 torr [5.01 ± 0.57 kPa]; p < .01), and mean esophageal pressure increased (7.7 ± 3.0 vs. 6.9 ± 3.0 cm H2O; p < .01) compared with the threshold triggering sensitivity. Conclusions: Autotriggering caused by cardiogenic oscillation is common in postcardiac surgery patients when flow triggering is used. Autotriggering occurred more often in patients with more dynamic circulation. Autotriggering caused respiratory alkalosis and hyperinflation of the lungs.

Mild elevation of urinary biomarkers in prerenal acute kidney injury

Prerenal acute kidney injury (AKI) is thought to be a reversible loss of renal function without structural damage. Although prerenal and intrinsic AKI frequently coexist in clinical situations, serum creatinine and urine output provide no information to support their differentiation. Recently developed biomarkers reflect tubular epithelial injury; therefore, we evaluated urinary biomarker levels in an adult mixed intensive care unit (ICU) cohort of patients who had been clinically evaluated as having prerenal AKI. Urinary L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), N-acetyl-β-D-glucosaminidase (NAG), and albumin in patients with prerenal AKI showed modest but significantly higher concentrations than in patients with non-AKI. We also conducted a proof-of-concept experiment to measure urinary biomarker excretion in prerenal AKI caused by volume depletion. Compared with cisplatinum and ischemia-reperfusion models in mice, volume depletion in mice caused a modest secretion of L-FABP and NGAL into urine with more sensitive response of L-FABP than that of NGAL. Although no histological evidence of structural damage was identified by light microscopy, partial kidney hypoxia was found by pimonidazole incorporation in the volume depletion model. Thus, our study suggests that new AKI biomarkers can detect mild renal tubular damage in prerenal acute kidney injury.

Urinary L-type fatty acid-binding protein as a new biomarker of sepsis complicated with acute kidney injury.

Objective:This study is aimed to examine whether urinary L-type fatty acid-binding protein can detect the severity of sepsis with animal sepsis models and septic shock patients complicated with established acute kidney injury. Design:Experimental animal models and a clinical, prospective observational study. Setting:University laboratory and tertiary hospital. Subjects and Patients:One hundred fourteen human L-type fatty acid-binding protein transgenic mice and 145 septic shock patients with established acute kidney injury. Interventions:Animals were challenged by abdominal (cecal ligation and puncture) and pulmonary (intratracheal lipopolysaccharide injection) sepsis models with different severities that were confirmed by survival analysis (n = 24) and bronchoalveolar lavage fluid analysis (n = 38). Measurements and Main Results:In animal experiments, significant increases of urinary L-type fatty acid-binding protein levels were induced by sepsis (severe cecal ligation and puncture 399.0 ± 226.8 &mgr;g/g creatinine [n = 12], less-severe cecal ligation and puncture 89.1 ± 25.3 [n = 11], sham 13.4 ± 3.4 [n = 10] at 6 hrs, p < .05 vs. sham; 200 &mgr;g of lipopolysaccharide 190.6 ± 77.4 &mgr;g/g creatinine [n = 6], 50 &mgr;g of lipopolysaccharide 145.4 ± 32.6 [n = 8], and saline 29.9 ± 14.9 [n = 5] at 6 hrs, p < .05 vs. saline). Urinary L-type fatty acid-binding protein predicted severity more accurately than blood urea nitrogen, serum creatinine, and urinary N-acetyl-d-glucosaminidase levels. In clinical evaluation, urinary L-type fatty acid-binding protein measured at admission was significantly higher in the nonsurvivors of septic shock with established acute kidney injury than in the survivors (4366 ± 192 &mgr;g/g creatinine [n = 68] vs. 483 ± 71 [n = 77], p < .05). Urinary L-type fatty acid-binding protein showed the higher value of area under the receiver operating characteristic curve for mortality compared with Acute Physiology and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) scores (L-type fatty acid-binding protein 0.994 [0.956–0.999], APACHE II 0.927 [0.873–0.959], and SOFA 0.813 [0.733–0.873], p < .05). Conclusions:Our results suggest that urinary L-type fatty acid-binding protein can be a useful biomarker for sepsis complicated with acute kidney injury for detecting its severity.

Postoperative polymyxin B hemoperfusion and mortality in patients with abdominal septic shock: a propensity-matched analysis.

Objectives:To examine the effect of postoperative polymyxin B hemoperfusion on mortality in patients with abdominal septic shock triggered by lower gastrointestinal tract perforation, identifying subpopulations of patients who may benefit from this treatment. Design:Propensity-matched analysis. Setting:We used a nationwide inpatient database in Japan. Patients:We included patients who are 18 years old or older hospitalized during a period of 34 months between July 2007 and October 2011, who had open abdominal surgery on the day of admission (day 0) for perforation of lower gastrointestinal tract, and who required noradrenaline and/or dopamine. We excluded patients who died on day 0 or 1 and patients starting polymyxin B hemoperfusion on day 2 or later. Measurements and Main Results:The main outcome was 28-day mortality. Of 2,925 eligible patients, 642 received one or two polymyxin B hemoperfusion sessions, starting the first one on day 0 or 1. Propensity score matching created a matched cohort of 1,180 patients (590 pairs with and without polymyxin B hemoperfusion). The 28-day mortality was 17.1% (101 of 590) in the polymyxin B hemoperfusion group and 16.3% (96 of 590) in the control group (p = 0.696). Subgroup analyses by number of polymyxin B hemoperfusion sessions (one or two), timing of polymyxin B hemoperfusion initiation (day 0 or 1), the use of noradrenaline, and number of dysfunctional organs (one to six) did not show any significant difference in 28-day mortality between the groups. Multiple logistic did not show a significant association between the use of polymyxin B hemoperfusion and 28-day mortality (adjusted odds ratio, 1.10; 95% CI, 0.80–1.51; p = 0.569). Age, end-stage renal disease requiring maintenance hemodialysis, the use of noradrenaline, and number of dysfunctional organs were positively associated with 28-day mortality. Conclusions:In this retrospective study, postoperative polymyxin B hemoperfusion did not show any survival benefit for the overall study population or any of the studied subgroups of patients with abdominal septic shock. A large multicentered prospective randomized trial is warranted to identify the true role of polymyxin B hemoperfusion in sepsis caused by Gram-negative bacteria.

Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice

Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1–deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.

Multi-DOF Forceps Manipulator System for Laparoscopic Surgery - Mechanism Miniaturized & Evaluation of New Interface

The Multi-DOF forceps manipulator we developed has two additional DOF of bending on the tip of forceps, and provides new surgical fields and techniques for surgeons. The most remarkable characteristics of the prototype described in this paper are: 1) the small diameter and the small radius of curvature of bending; 2) the confirmation of perfect cleanness and sterilization of this manipulator. In this paper, we will show some new mechanisms of the forceps manipulator. Firstly, we made new mechanism of bending forceps. Using the mechanism, we made new prototype of forceps manipulator which diameter is 5mm. Secondly, we developed new concept of man-machine interface for the system. It will show the new control method and surgeons can operate surgeries with more dexterity and without confusion. We evaluated the system including new interface on typical laparosurgical procedure using simulator, and confirmed the effectiveness of this concepts.

Health care costs related to out-of-hospital cardiopulmonary arrest in Japan

OBJECTIVES Although cost analyses for emergency care are essential, data on costs of care for out-of-hospital cardiopulmonary arrest (OHCA) are scarce. The present study aimed to analyze health care costs related to OHCA using a nationwide administrative database in Japan. METHODS Using the Diagnosis Procedure Combination database in Japan, we identified OHCA patients who were transported to 779 emergency medical centres between July and December in 2008 and 2009. We assessed patient survival and discharge status, receipt of specific treatments, and costs of in-hospital care. RESULTS A total of 21,750 OHCA patients were identified. Overall, 59.6% were males, and the average age was 70.3 years. Of them, 1394 (6.4%) resulted in death without attempted resuscitation after hospital arrival (Group A), 14,973 (69.0%) died on admission day despite resuscitation attempts (Group B), 3680 (17.0%) died at ≥2 days after admission despite resuscitation attempts (Group C), 785 (3.6%) survived and were discharged to home (Group D) and 873 (4.0%) survived and discharged to other than home (Group E). The median total costs were