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Objective: The Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During Post-Cardiac Arrest Care (HYBRID) II trial (jRCTs031180352) suggested that hydrogen inhalation may reduce post-cardiac arrest brain injury (PCABI). However, the combination of hypothermic target temperature management (TTM) and hydrogen inhalation on outcomes is unclear. The aim of this study was to investigate the combined effect of hydrogen inhalation and hypothermic TTM on outcomes after out-of-hospital cardiac arrest (OHCA)., Design: Post hoc analysis of a multicenter, randomized, controlled trial., Setting: Fifteen Japanese ICUs., Patients: Cardiogenic OHCA enrolled in the HYBRID II trial., Interventions: Hydrogen mixed oxygen (hydrogen group) versus oxygen alone (control group)., Measurements and Main Results: TTM was performed at a target temperature of 32-34°C (TTM32-TTM34) or 35-36°C (TTM35-TTM36) per the institutional protocol. The association between hydrogen + TTM32-TTM34 and 90-day good neurologic outcomes was analyzed using generalized estimating equations. The 90-day survival was compared between the hydrogen and control groups under TTM32-TTM34 and TTM35-TTM36, respectively. The analysis included 72 patients (hydrogen [ n = 39] and control [ n = 33] groups) with outcome data. TTM32-TTM34 was implemented in 25 (64%) and 24 (73%) patients in the hydrogen and control groups, respectively ( p = 0.46). Under TTM32-TTM34, 17 (68%) and 9 (38%) patients achieved good neurologic outcomes in the hydrogen and control groups, respectively (relative risk: 1.81 [95% CI, 1.05-3.66], p < 0.05). Hydrogen + TTM32-TTM34 was independently associated with good neurologic outcomes (adjusted odds ratio 16.10 [95% CI, 1.88-138.17], p = 0.01). However, hydrogen + TTM32-TTM34 did not improve survival compared with TTM32-TTM34 alone (adjusted hazard ratio: 0.22 [95% CI, 0.05-1.06], p = 0.06)., Conclusions: Hydrogen + TTM32-TTM34 was associated with improved neurologic outcomes after cardiogenic OHCA compared with TTM32-TTM34 monotherapy. Hydrogen inhalation is a promising treatment option for reducing PCABI when combined with TTM32-TTM34., Competing Interests: Dr. Tamura’s institution received funding from the Taiyo Nippon Sanso Corporation, the Japanese Society for Promotion of Science, and the Marumo Memorial Foundation Grant for Emergency Medicine Research. Drs. Tamura and Suzuki disclosed off-label use of hydrogen gas. Dr. Narumiya disclosed work for hire. Dr. Homma has disclosed that he does not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Aim: We aimed to investigate the association between estimated glomerular filtration rate and prognosis in out-of-hospital cardiac arrest patients and explore the heterogeneity of the association., Methods: Patients experiencing out-of-hospital cardiac arrest due to medical causes and registered in the JAAM-OHCA Registry between June 2014 and December 2019 were stratified into shockable rhythm, pulseless electrical activity, and asystole groups according to the cardiac rhythm at the scene. The primary outcome was a 1-month favorable neurological status. Adjusted odds ratios with 95% confidence intervals were calculated to investigate the association between estimated glomerular filtration rate and outcomes using a logistic model., Results: Of the 19,443 patients included, 2769 had initial shockable rhythm at the scene, 5339 had pulseless electrical activity, and 11,335 had asystole. As the estimated glomerular filtration rate decreased, the adjusted odds ratio for a 1-month favorable neurological status decreased among those with initial shockable rhythm (estimated glomerular filtration rate, adjusted odds ratio [95% CI]: 45-59 mL/min/1.73 m 2 , 0.61 [0.47-0.79]; 30-44 mL/min/1.73 m 2 , 0.45 [0.32-0.62]; 15-29 mL/min/1.73 m 2 , 0.35 [0.20-0.63]; and <15 mL/min/1.73 m 2 , 0.14 [0.07-0.27]). Estimated glomerular filtration rate was associated with neurological outcomes in patients aged <65 years with initial shockable rhythm but not in those aged >65 years or patients with initial pulseless electrical activity or asystole., Conclusion: The estimated glomerular filtration rate is associated with neurological prognosis in out-of-hospital cardiac arrest patients with initial shockable rhythm at the scene but not in those with initial non-shockable rhythm., Competing Interests: The authors declare no conflict of interests for this article., (© 2024 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background: The TiPS65 score is a validated scoring system used to predict neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients with shockable rhythm treated with extracorporeal cardiopulmonary resuscitation (ECPR). This study aimed to assess the predictive performance of the TiPS65 score in OHCA patients with initial non-shockable rhythm treated with ECPR., Methods: This was a secondary analysis using the JAAM-OHCA registry, a multicenter prospective cohort study. The study included adult OHCA patients with initial non-shockable rhythm who underwent ECPR. The TiPS65 score assigned one point to each of four variables: time to hospital ≤25 minutes, pH value ≥7.0 on initial blood gas assessment, shockable on hospital arrival, and age younger than 65 years. Based on the sum score, the predictive performance for 1-month survival and favorable neurological outcomes, defined as the Cerebral Performance Category 1 or 2, was evaluated., Results: Among 57,754 patients in the registry, 370 were included in the analysis. The overall one-month survival and favorable neurological outcome were 11.1% (41/370) and 4.2% (15/370), respectively. The 1-month survival rates based on the TiPS65 score were as follows: 11.2% (12/107) for 0 points, 9.3% (14/150) for 1 point, 10.0% (9/90) for 2 points, and 26.1% (6/23) for ≥3 points. Similarly, the 1-month favorable neurological outcomes were: 5.6% (6/107) for 0 points, 2.7% (4/150) for 1 point, 4.4% (4/90) for 2 points, and 4.3% (1/23) for ≥3 points. The area under the curve was 0.535 (95% CI: 0.437-0.630) for 1-month survival and 0.530 (95% CI: 0.372-0.683) for 1-month neurological outcome., Conclusion: This study demonstrates that the TiPS65 score has limited prognostic performance among OHCA patients with initial non-shockable rhythm treated with ECPR. Further research is warranted to develop a predictive tool specifically focused on OHCA with initial non-shockable rhythm to aid in determining candidates for ECPR., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘YO has received a research grant from the ZOLL Foundation and an overseas scholarship from the FUKUDA Foundation for medical technology and the International medical research foundation. These organizations have no role in conducting this research. MEHO reports grants from the Laerdal Foundation, Laerdal Medical, and Ramsey Social Justice Foundation for funding of the Pan-Asian Resuscitation Outcomes Study an advisory relationship with Global Healthcare SG, a commercial entity that manufactures cooling devices; and funding from Laerdal Medical on an observation program to their Community CPR Training Centre Research Program in Norway. MEHO is a Scientific Advisor to TIIM Healthcare SG and Global Healthcare SG. MEHO is a part of the editorial board.’., (© 2023 The Author(s).)

We report the formation of M-M dimers (M = Pt or Pd) of cationic [M(dpb)(CH 3 CN)] + [dpbH = 1,3-di(2-pyridyl)benzene] and neutral [M(dpb)Cl] complexes resulting from the rapid freezing of solutions. Dimers based on M-M dz 2 overlap were found to preferentially form rather than the thermodynamically favored head-to-tail π-stacking structures typically observed in the crystalline state. Kinetic dimers in glassy frozen solutions generated broad metal-metal-to-ligand charge-transfer emissions within the range of 600-800 nm at 77 K. These emissions were red-shifted relative to monomer emissions. As expected, the degree of aggregation of these complexes was affected by the concentration in each solution. Photoexcitation evidently accelerated Pt-Pt dimerization even at ambient temperature. Electrostatic attraction between [Pt(dpb)Cl] + and [Pt(dpb)Cl] - ions resulting from disproportionation due to photoinduced electron transfer is thought to have driven excimer formation. [Pt(dpb)(CH 3 CN)]OTf (OTf - = trifluoromethanesulfonate ion) and its Pd(II) analogue were determined to have isostructural crystals, but a Pd-Pd stacked polymorph was not observed and the photophysics of the two complexes are evidently different.

Aim: Emergency front of neck access (eFONA), such as scalpel cricothyroidotomy, is a rescue technique used to open the airway during "cannot intubate, cannot oxygenate" situations. However, little is known about the adverse events associated with the procedure. This study aimed to describe the adverse events that occur in patients who undergo eFONA and their management., Methods: This retrospective observational cohort study included emergency patients who underwent eFONA between April 2012 and August 2020. We described the patients' characteristics and the adverse events during or immediately after the procedure., Results: Among 75,529 emergency patients during the study period, 31 (0.04%) underwent an eFONA. The median (interquartile range) age was 53 (39-67) years, and 23 patients (74.2%) were men. Of all cases, 13 (41.9%) experienced adverse events. Of these, three cases (23.2%) were cephalad misplacement of the intubation tube, one case (7.7%) was cuff injury, one case (7.7%) was tube obstruction due to vomiting, and one case (7.7%) was tube kink. In cases with these adverse events, the initial attempt of eFONA failed, and alternative immediate action was necessary to secure the airway., Conclusion: This single-center retrospective observational study described several adverse events of eFONA. In particular, it is important to understand the possible life-threatening adverse events that lead to failure of securing airways such as cephalad displacement, tube obstruction, and tube kink and respond promptly to ensure a secure definitive airway for patients' safety., (© 2022 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Purpose: Avoiding body temperature (BT) abnormalities has been emphasized in trauma care, and BT correction in the initial treatment period may improve patient outcome. However, the effect of hyperthermia at hospital arrival on mortality in trauma patients is unclear. This study aimed to identify the association between BT and in-hospital mortality among adult trauma patients., Methods: This was a retrospective analysis of a multi-centre prospective cohort study. Data were obtained from the Japan Trauma Data Bank (JTDB). Adult trauma patients who were transferred directly from the scene of injury to the hospital and registered in the JTDB between January 2004 and December 2017 were included. The primary outcome was the association between BT at hospital arrival and in-hospital mortality. BT at hospital arrival was classified by 1 °C strata. We conducted multivariable logistic regression analyses to calculate the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality for each BT group using 36.0-36.9 °C as a reference., Results: Overall, 153,117 patients were included. The total mortality rate was 7% (n = 10,118). The adjusted OR for in-hospital mortality for < 35.0 °C was 1.65 (95% CI 1.51-1.79, p < 0.001), 35.0-35.9 °C was 1.33 (95% CI 1.25-1.41, p < 0.001), 37.0-37.9 °C was 0.99 (95% CI 0.91-1.07, p = 0.639), 38.0-38.9 °C was 1.30 (95% CI 1.08-1.56, p = 0.007) and > 39.0 °C was 1.62 (95% CI 1.18-2.22, p = 0.003) compared to that for normothermia., Conclusions: Our results reveal that hypothermia and hyperthermia at hospital arrival are associated with increased in-hospital mortality in adult trauma patients., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to determine the association between cardiopulmonary resuscitation (CPR) under the coronavirus 2019 (COVID-19) safety protocols in our hospital and the prognosis of out-of-hospital cardiac arrest (OHCA) patients, in an urban area, where the prevalence of COVID-19 infection is relatively low. This was a single-center, retrospective, observational, cohort study conducted at a tertiary critical care center in Kyoto City, Japan. Adult OHCA patients arriving at our hospital under CPR between January 1, 2019, and December 31, 2020 were included. Our hospital implemented a revised resuscitation protocol for OHCA patients on April 1, 2020 to prevent COVID-19 transmission. This study defined the conventional CPR period as January 1, 2019 to March 31, 2020, and the COVID-19 safety protocol period as April 1, 2020 to December 31, 2020. Throughout the prehospital and in-hospital settings, resuscitation protocols about wearing personal protective equipment and airway management were revised in order to minimize the risk of infection; otherwise, the other resuscitation management had not been changed. The primary outcome was hospitalization survival. The secondary outcomes were return of spontaneous circulation after hospital arrival and 1-month survival after OHCA occurrence. The adjusted odds ratios with 95% confidence intervals (CI) were calculated for outcomes to compare the two study periods, and the multivariable logistic model was used to adjust for potential confounders. The study analyzed 443 patients, with a median age of 76 years (65-85), and included 261 men (58.9%). The percentage of hospitalization survivors during the entire research period was 16.9% (75/443 patients), with 18.7% (50/267) during the conventional CPR period and 14.2% (25/176) during the COVID-19 safety protocol period. The adjusted odds ratio for hospitalization survival during the COVID-19 safety protocol period was 0.61 (95% CI 0.32-1.18), as compared with conventional CPR. There were no cases of COVID-19 infection among the staff involved in the resuscitation in our hospital. There was no apparent difference in hospitalization survival between the OHCA patients resuscitated under the conventional CPR protocol compared with the current revised protocol for controlling COVID-19 transmission.

Aims: Initial cardiac rhythm, particularly shockable rhythm, is a key factor in resuscitation for out-of-hospital cardiac arrest (OHCA) patients. The purpose of this study was to clarify the association between cardiac rhythm conversion and neurologic prognosis in OHCA patients with initial shockable rhythm at the scene., Methods and Results: The study included adult patients with OHCA due to medical causes with pre-hospital initial shockable rhythm and who were still in cardiac arrest at hospital arrival. Multiple logistic regression analysis was conducted to identify the adjusted odds ratios (AORs) and 95% confidence interval (CI) of cardiac arrest rhythm at hospital arrival for 1-month favourable neurologic status and 1-month survival, adjusted for potential confounders. Of 34 754 patients in the 2014-2017 JAAM-OHCA Registry, 1880 were included in the final study analysis. The percentages of 1-month favourable neurologic status for shockable rhythm, pulseless electrical activity (PEA), and asystole at hospital arrival were 17.4% (137/789), 3.6% (18/507), and 1.5% (9/584), respectively. The AORs for 1-month favourable neurologic status comparing to OHCA patients who maintained shockable rhythm at hospital arrival were PEA, 0.19 (95% CI, 0.11-0.32) and asystole, 0.08 (95% CI, 0.04-0.16), respectively., Conclusion: Findings showed that the 1-month neurologic outcome in OHCA patients who converted to non-shockable rhythm at hospital arrival was very poor compared with patients who had sustained shockable rhythm. Also, patients with conversion to PEA had better neurologic prognosis than conversion to asystole., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aim: This study aimed to identify the association between total visitation restriction because of the coronavirus 2019 (COVID-19) pandemic and the incidence of delirium for emergency inpatients., Methods: This was a single-center, retrospective, observational cohort study conducted at a tertiary critical care center in urban Kyoto, Japan. Adult emergency patients hospitalized between January 1, 2019, and June 30, 2020, were recruited. In response to the COVID-19 pandemic, the authors' hospital began restricted visitation on March 28, 2020. This study defined before visitation restriction as January 1, 2019, through March 31, 2020, and after visitation restriction as April 1, 2020, through June 30, 2020. We did not restrict emergency services, and there were no changes in the hospital's routine, except for visitation restrictions. The primary outcome was the incidence of delirium. The adjusted odds ratio (AOR) with 95% confidence interval (CI) for delirium incidence was calculated to compare the before and after visitation restriction periods, and the logistic model was used to adjust for seven variables: age, sex, ward type on admission, primary diagnosis, ventilator management, general anesthesia surgery, and dementia., Results: Study participants were 6264 patients, median age 74 years (56-83), and 3303 men (52.7%). The total delirium incidence in entire research period was 2.5% (158 of 6264 patients), comprising 1.8% (95/5251) before visitation restriction and 6.2% (63/1013) after visitation restriction. The AOR for delirium incidence was 3.79 (95% CI, 2.70-5.31) after visitation restriction versus before visitation restriction. Subgroup analysis showed no apparent interaction for delirium incidence., Conclusion: Visitation restriction was associated with an increased incidence of delirium in emergency inpatients., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Objectives: To examine the association between body temperature (BT) on hospital arrival and in-hospital mortality among paediatric trauma patients., Design: A retrospective cohort study., Setting: Japan Trauma Data Bank (JTDB, which is a nationwide, prospective, observational trauma registry with data from 235 hospitals)., Participants: Paediatric trauma patients <16 years old who were transferred directly from the scene of injury to the hospital and registered in the JTDB from January 2004 to December 2017 were included. We excluded patients >16 years old and those who developed cardiac arrest before or on hospital arrival., Primary Outcome: The association between BT on hospital arrival and in-hospital mortality. We conducted multivariate logistic regression analyses to calculate the adjusted ORs, with their 95% CIs, of the association between BT and in-hospital mortality., Results: A total of 9012 patients were included (median age: 9 years (IQR, 6.0-13.0 years), mortality: 2.5% (mortality number was 226 in total 9012 patients)). In the multivariate logistic regression analysis, the corresponding adjusted ORs of BT <36.0°C and BT ≥37.0°C, relative to a BT of 36°C-36.9°C, for in-hospital mortality were 2.83 (95% CI: 1.85 to 4.33) and 0.93 (95% CI: 0.53 to 1.63), respectively., Conclusions: In paediatric patients with hypothermia (BT <36.0°C) on hospital arrival, a clear association with in-hospital mortality was observed; no such association was observed between higher BT values (≥37.0°C) and outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: This study aims to identify the clinical factors that can predict the requirement of massive transfusion among patients with postpartum hemorrhage (PPH)., Methods: Consecutive anonymized patients with PPH who were treated at the emergency department of our perinatal medical center were examined. Patients who had received transfusions before admission, those who had cardiac arrest on arrival, and those without history of blood gas analysis were excluded. Our primary outcome was the requirement of massive transfusion defined as packed red blood cells of ≥10 units/24 h. Univariable logistic analysis was carried out to identify the odds ratio and 95% confidence interval (CI) of the explanatory variables for the outcome., Results: A total of 31 patients (massive transfusion, n  = 19) were included in the main analysis. The crude odds ratio for fibrinogen per mg/dL and lactate per mmol/L were calculated as 0.98 (95% CI, 0.97-0.99) and 1.62 (95% CI, 1.08-3.02), respectively. The area under the curves for fibrinogen and lactate were 0.814 and 0.734, respectively, and optimal cut-off values for fibrinogen and lactate were 211 mg/dL and 4 mmol/L, respectively., Conclusion: These findings suggest that lactate and fibrinogen can be predictors for the requirement of massive transfusion in patients with PPH., (© 2019 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Instantaneous rigor is the immediate appearance of rigor mortis after cardiac arrest. To our knowledge, no previous reports exist on resuscitation of such patients. A young athlete suddenly collapsed with cardiac arrest during a marathon; his legs stiffened with instantaneous rigorlike stiffness. This stiffening provoked hyperkalemia, rhabdomyolysis, and multiple organ failure. We decided to amputate both legs, with venoarterial extracorporeal membrane oxygenation support. The patient recovered and was discharged without neurologic impairment. This rare case highlights the potentially significant effect of instantaneous rigor., (Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

A previously healthy 55-year-old man with H1N1 influenza A presented with severe respiratory failure and cardiac arrest. Following the return of spontaneous circulation, venovenous extracorporeal membrane oxygenation was required to maintain oxygenation. On day 2, bronchoscopy revealed a bloody bronchial cast obstructing the right main bronchus. A pathological examination revealed that it was composed of intrabronchial and intra-alveolar hemorrhagic tissue. Unfortunately, the patient died due to severe brain ischemia; a subsequent autopsy revealed marked alveolar hemorrhage. It is possible that anticoagulant therapy, alveolar collapse, and neuromuscular blocking agents provoked cast development in this case.

Background: Catecholamine agents are commonly used to support circulation; however, they may cause unexpected hypotension in a special situation. Here we describe the first unexpected case of hypotension in response to catecholamine agents., Case Presentation: A 29-year-old Japanese man with schizophrenia was transferred to our emergency department. He was in shock and in coma. After fluid resuscitation, we induced catecholamine agents; however, his blood pressure decreased to 59/40 mmHg in response to catecholamine infusion. On the other hand, after we started vasopressin, his blood pressure markedly improved, and he finally became stable. On day 2, he admitted to ingesting a large amount of risperidone, and we diagnosed risperidone overdose. We believe that this unexpected hypotension in response to catecholamine infusion was caused by an α-adrenergic blockade effect of risperidone. Animal experiments proved that the simultaneous administration of adrenaline with an α-adrenergic blockade provoked a fall in blood pressure; this phenomenon is called "adrenaline reversal." In our case, catecholamine infusion under the α-adrenergic blockade effect of risperidone might have caused a fall in blood pressure in the same mechanism; we call this phenomenon "catecholamine reversal." In such a situation, because the mechanism of vasopressin is different from that of catecholamine, we recommend vasopressin for maintaining the blood pressure., Conclusions: We described the first clinical case of "catecholamine reversal" and highlighted that if unexpected hypotension occurs in response to catecholamine infusion, we should suspect the use of α-adrenergic antagonists. In such situations, we should consider the administration of vasopressin instead.

Poikilothermia is a fundamental symptom of acute limb ischemia (ALI) and is known as "6Ps". Herein, we present the visualization of poikilothermia caused by ALI using handheld thermography. We believe that handheld thermography could be useful to assess poikilothermia objectively as a supplementary method to physical examination.

Background: Resuscitative balloon occlusion of the aorta (REBOA) can maintain hemodynamic stability during hemorrhagic shock after a following torso injury, although inappropriate balloon placement may induce brain or visceral organ ischemia. External anatomical landmarks [the suprasternal notch (SSN) and xiphoid process (Xi)] are empirically used to implement REBOA in zone 1. We aimed to confirm if these landmarks were useful for determining a balloon catheter length for safe implementation of REBOA in zone 1 without using fluoroscopy., Method: We selected 25 successive adult blunt trauma cases requiring contrast-enhanced chest/abdominal computed tomography (CT) treated at our emergency department (in an urban area of Kyoto city, Japan) between October 1, 2016 and January 31, 2017. We retrospectively evaluated anonymized CT images. We used three-dimensional multiplanar reconstructions to measure the length along the aorta's central axis, from the bilateral common femoral arteries (FA) to the celiac trunk (CeT) (FA-CeT) and to the origin of the left subclavian artery (LSCA) (FA-LSCA). Volume-rendering reconstruction images were used to measure the external distance from common FAs to SSN (FA-SSN) and to Xi (FA-Xi)., Result: FA-LSCA was significantly longer than FA-SSN. FA-CeT was significantly shorter than FA-Xi., Discussion: Based on these results, the REBOA balloon catheter should be shorter than FA-SSN, and longer than FA-Xi to avoid placement outside zone 1. The advantages of this method are that it can rapidly and easily predict a safe balloon catheter length, and it reflects each patient's individual torso height., Conclusion: To safely implement REBOA, the balloon catheter length should be shorter than FA-SSN and longer than FA-Xi. We believe that these anatomical landmarks are good references for safe implementation of REBOA in zone 1 without radiographic guidance.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an emergency procedure to manage severe hemorrhagic shock from torso injury but can cause severe ischemia of the lower extremities. However, lower extremity ischemia occurring as a complication of REBOA has been rarely reported. We describe the severe lower extremity ischemia caused by REBOA with a 12-Fr sheath in a small-built patient., Case Representation: The patient was a 16-year-old male who developed severe hemorrhagic shock due to abdominal blunt trauma. Following REBOA with a 12-Fr sheath on the right femoral artery, an emergency laparotomy and angiography to control the hemorrhage were performed. Twenty-eight hours after admission, suspecting lower extremity ischemia and compartment syndrome, we removed the sheath with a manual maneuver and performed fasciotomy. The limb ischemia was thus partially resolved. However, amputation was necessary because of ischemic necrosis on day 32. Our patient was physically small, and the diameter of his femoral artery on the contralateral site of sheath placement was also small. Therefore, disproportion of the sheath and femoral artery sizes may have caused the ischemic complication., Conclusion: Our experience highlights the importance of appropriate size selection for the sheath in line with the target vessel. We also recommend postoperative monitoring of limb perfusion in such cases with the use of near-infrared spectroscopy to facilitate the early detection of ischemia.

Innominate artery injury is a rare, but catastrophic complication of tracheostomy. We present a case of severe hemorrhagic shock in a 79-year-old male with innominate artery injury that occurred during tracheostomy. Despite temporary innominate artery isolation, the regional forehead saturation was 60 % without laterality. Because adequate cerebral blood flow was apparently maintained through collateral flow, we ligated the innominate, right carotid, and subclavian arteries. We confirmed adequate blood flow to the brain and the right subclavian artery through collateral circulation after ligation using computed tomographic angiography. A damage control management, which involves ligating the injured innominate artery to arrest hemorrhage and monitoring regional forehead saturation for brain ischemia, can be a considerable procedure for the treatment of severe hemorrhagic shock due to innominate artery injury.

Background: Direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP) could improve the hemodynamic status of septic shock patients. As PMX-DHP is an invasive and costly procedure, it is desirable to estimate the therapeutic effect before performing the therapy. However, it is still unclear when this therapy should be started and what type of sepsis it should be employed for. In this study, we retrospectively examined the clinical effect of patients treated with PMX-DHP by using central venous pressure (CVP)., Methods: Seventy patients who received PMX-DHP for septic shock during the study period were recruited and divided into a low CVP group ( n  = 33, CVP < 12 mmHg) and a high CVP group ( n  = 37, CVP≧12 mmHg). The primary endpoint was vasopressor dependency index at 24 hours after starting PMX-DHP, and the secondary endpoint was the 28-day survival rate. Additionally, we performed a multivariate linear regression analysis on the difference in the vasopressor dependency index., Results: The vasopressor dependency index significantly improved at 24 h in the low CVP group (0.33 to 0.16 mmHg -1 ; p  < 0.01) but not in the high CVP group (0.43 to 0.34 mmHg -1 ; p  = 0.41), and there was a significant difference between the two groups in the index at 24 h ( p  = 0.02). The 28-day survival rate was higher in the low CVP group (79 vs. 43 %; p  < 0.01). Multivariate linear regression analysis showed that CVP ( p  = 0.04) was independently associated with the difference in the vasopressor dependency index., Conclusions: Our study indicates that the clinical effect of PMX-DHP for septic shock patients with higher CVP (≧12 mmHg) might be limited and that the initial CVP when performing PMX-DHP could function as an independent prognostic marker for the hemodynamic improvement.

Aims: Anemia, which might contribute to pathogenesis of kidney dysfunction, is a common finding in patients with type 2 diabetes. The aim of this study was to investigate if hemoglobin concentration is associated with the degree of change in urinary albumin-creatinine ratio or the development of albuminuria in patients with type 2 diabetes., Methods: We measured hemoglobin concentration in 470 (296 men and 174 women) consecutive type 2 diabetic patients without albuminuria. We performed a follow-up study to assess the progression or development of albuminuria, the interval of which was 3.0 years. Then we evaluated relationships between hemoglobin concentration and albuminuria, using multivariate linear regression analyses and logistic regression analyses., Results: Eighty four patients developed albuminuria during follow-up duration. In multivariate analyses, hemoglobin concentration was negatively associated with a change in urinary albumin-creatinine ratio in men (ß = -0.259, P = 0.0002) and women (ß = -0.194, P = 0.030). Moreover, multivariate adjusted odds ratio associated with 1 g/L in hemoglobin for the development of albuminuria was 0.93 (95% confidence interval; 0.89-0.96) in men and 0.94 (95% confidence interval; 0.88-0.99) in women, respectively. And, multivariate analyses revealed that adjusted odds ratios for the development of albuminuria were 4.78 (95% confidence interval; 1.65-13.91) in men and 4.62 (95% confidence interval; 1.34-16.68) in women with anemia (hemoglobin < 130 g/L for men and < 120 g/L for women), which were higher than those without anemia., Conclusions: Low hemoglobin concentration could be a predictor for the progression and development of albuminuria in patients with type 2 diabetes.

Background: The klotho gene and its protein product are mainly expressed in the kidney. The klotho protein induces suppression of multiple aging-related phenotypes, and homozygous klotho gene mutant mice display various senescent morbidity. Chronic inhibition of nitric oxide synthase (NOS) induces arteriosclerosis, while HMG-CoA reductase inhibitors (statins) have pleiotropic vascular protective effects besides cholesterol lowering. Therefore, the present studies were performed to determine whether chronic NOS blockade would affect anti-ageing klotho protein expression. In addition, the effects of statins on klotho protein expression and arteriosclerosis in these rats were investigated., Methods: Forty-two rats were divided into 6 groups as follows: (1) control, (2) NOS blockade, (3) atorvastatin (10 mg/kg/day), (4) pitavastatin (3 mg/kg/day), (5) NOS blockade+atorvastatin, (6) NOS blockade+pitavastatin. To induce arteriosclerosis further, a cuff was placed around the left femoral artery in each rat. After 4 weeks observation, rats were killed and renal klotho expression and the level of arteriosclerosis were examined., Results: The rats of chronic NOS inhibition developed hypertension, while statin treatment did not affect blood pressure in the rats with or without NOS blockade. Despite statin treatment, plasma levels of lipids did not differ among 6 groups. Immunohistochemical staining revealed that klotho protein was localized in the renal tubules. Chronic NOS inhibition markedly reduced renal klotho protein expression, while treatment with atorvastatin or pitavastatin completely prevented the reduction of klotho expression induced by NOS inhibition. In addition, statin treatment significantly improved arteriosclerotic lesions induced by NOS inhibition and cuff placement., Conclusion: Since statin treatment did not alter blood pressure or serum lipid profiles, a novel vascular protective effect of statins via enhancing anti-aging klotho protein expression is suggested.

Endocardial cells and cardiomyocytes differentiate from the cardiogenic mesoderm at about the same time during development. Although in vitro embryonic stem (ES) cell systems have been used to study the differentiation of various types of cell lineages, including cardiomyocytes, smooth muscle cells, and vascular endothelial cells, differentiation of endocardial cells, or endocardiogenesis, has not been well reported, because of a lack of specific molecular markers. In our search for cardiogenesis-associated genes expressed in embryoid bodies, we found several genes expressed in the heart region of mouse embryos, but not in cardiomyocytes. To identify the cell types expressing these genes, CD31(+) cells were taken from mouse embryos on embryonic day (E)8.5 and E9.5 and sorted, then their transcripts were analyzed using quantitative RT-PCR analyses. In those embryos, Gata4 and Nfatc1, as well as newly identified Cgnl1 and Dok4 were found to be preferentially expressed in endocardial cells, but not in yolk sac endothelial cells, while Cdh5 and Kdr were expressed in both cardiac and yolk sac endothelial cells. Immunohistochemical analyses of embryoid bodies revealed that some CD31(+) cells co-expressing Gata4 and Nfatc1 were located in close proximity to cardiomyocytes. These results suggest that embryoid bodies express endocardial specific genes and likely generate endocardial cells along with cardiomyocytes. Further, they indicate that these new marker genes are useful to study the origin and induction of endocardial cells, and identify other endocardial markers.

Cardiogenesis can be induced in vitro in ES cells, though it is difficult to distinguish cardiac-specific genes, since embryoid bodies simultaneously differentiate into multiple lineages. In the present study, transient serum removal during culture greatly enhanced cardiogenesis, and reduced generation of endothelial and hematopoietic cells. Using DNA microarray analysis of 24 differentiated sample cultures including cardiogenesis-enhanced cells, we successfully selected genes up-regulated in embryoid bodies that had undergone cardiogenic differentiation. Besides contractile protein genes, cardiac transcriptional regulatory genes, such as Nkx2-5, Gata4/5, Mef2c, and Myocd, were primary constituents of the first 100 genes chosen as cardiogenesis-associated genes. Further, whole mount in situ hybridization analysis of 13 genes containing non-characterized ones confirmed that most of them were specifically expressed in the heart region of mouse embryos from E9.5-10.5. Based on our results, we consider that the present profiling method may be useful to identify novel genes important for cardiac development.

We examined the relationship between structural changes of the aorta and pulse wave velocity (PWV), and the effects of antihypertensive treatments on PWV in N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated rats. Twelve-week-old Wistar-Kyoto (WKY) rats were divided into the following groups, all of which received drug treatment in their drinking water: an untreated control group (n = 36), an L-NAME-treated group (0.7 mg/ml) (n = 32), an L-NAME and angiotensin converting enzyme (ACE) inhibitor (ACEI)-treated group (imidapril: 0.4 mg/ml) (n = 8), and an L-NAME and hydralazine-treated group (0.2 mg/ml) (n = 10). PWV was measured at the same blood pressure (BP) level as in the control group and the wall-to-lumen ratio of the thoracic aorta was evaluated in all groups. In the L-NAME group, PWV increased compared with the value in the control group, at the same time that BP was increasing. After the third day of treatment, PWV was higher in the L-NAME group than in the control group after adjusting BP to the control level, while the wall-to-lumen ratios were equal between the two groups. After the first week of treatment, not only the adjusted PWV, but also the wall-to-lumen ratios were greater in the L-NAME group than in the control group. With administration of antihypertensive agents, both PWV and the thickening of the aortic wall were reduced, but there was no significant difference between the ACEI and hydralazine-treated groups. In conclusion, in a rat model of nitric oxide (NO) synthesis inhibition, the increase in PWV preceded the vascular structural changes, while antihypertensive treatment reduced both changes. There was no significant difference between treatments with ACEI and hydralazine in this model.

We report a case of non-Hodgkin lymphoma (NHL) with acute renal failure. A 62-year-old man was admitted to our hospital on March 8, 2002 with leg edema and dyspnea on effort. About 3 weeks before admission, he was found to have slightly high serum creatinine (Cr) and high lactate dehydrogenase (LDH) levels by another home doctor. Physical examination revealed anemic conjunctivae and leg edema, but the urinary volume was preserved. Blood examination showed high BUN (64 mg/dl) and Cr levels (3.91 mg/dl). Urinary analysis showed proteinuria (1.05 g/day) and high BMG (14,434/microg/day) and NAG (4.55 U/day) levels, suggesting severe tubulointerstitial injury. On ultrasonography of the kidney, the bilateral kidneys showed marked swelling without hydronephrosis. To investigate the genesis of renal failure, we performed a renal biopsy. The specimen showed normal glomeruli, but a large number of cells infiltrated in the tubulointerstitial area with normal tubulointerstitial structure. The cells stained positively with anti-leukocyte antigen and L26 (B cell marker), and negatively with cytokeratin and UCHL-1 (T cell marker). These findings indicate that the interstitial cells were non-Hodgkin lymphoma with B cell diffuse large cells. Chemotherapy was performed with VAD (vincristine sulfate, doxorubicin hydrochloride, dexamethasone) considering his renal dysfunction. To avoid tumor lysis syndrome after chemotherapy, hemodialysis was performed on days 1-4 after the initiation of chemotherapy. After a series of chemotherapy, the urinary volume increased and serum Cr levels decreased to 2 mg/dl. After additional therapy with 4 courses of CHOP, he improved and was discharged on day 180 after admission.

Background: There is evidence of altered vascular endothelial function in women with preeclampsia as well as in the endothelial cells from umbilical vessels of preeclamptic pregnancies. Matrix metalloproteinase (MMP)-2 is elevated in the plasma of preeclamptic women and is a mediator of vascular reactivity; however, whether MMP-2 release is altered in preeclamptic endothelial cells is unknown. We hypothesize that MMP-2 release is enhanced in endothelial cells from preeclamptic compared with uncomplicated pregnancies and that this phenomenon may be mediated by an oxygen-dependent mechanism. Our specific hypothesis is that cells from normal pregnancies will demonstrate enhanced MMP-2 release at low oxygen (< 0.5%, 2%) compared to high oxygen (20%), thus mimicking the behavior of preeclamptic cells., Methods: Human umbilical vein endothelial cells (HUVECs) from preeclamptic pregnancies (n = 4) and normal pregnancies (n = 4) were incubated for 12 hr in standard culture conditions (20% oxygen). In a separate series of experiments, HUVECs from normal pregnancies (n = 6) were incubated for 12 hr at < 0.5%, 2%, and 20% oxygen. Supernatants were analyzed for MMP-2 and tissue inhibitors of metalloproteinases (TIMP)-1 and -2., Results: The HUVECs from women with preeclampsia demonstrated significantly enhanced release of MMP-2 (p < 0.05), TIMP-1 (p < 0.001), and TIMP-2 (p = 0.01) compared to normal cells. MMP-2 release from HUVECs from uncomplicated pregnancies was significantly elevated at 2% oxygen compared to < 0.5% and 20% oxygen (p < 0.05). TIMP-1 and -2 secretion was not altered with varying oxygen., Conclusions: Preeclamptic endothelial cells demonstrate significantly enhanced MMP-2, TIMP-1 and TIMP-2 release compared to normal cells. Our data show that there are significant effects of oxygen tension on MMP-2 release from normal cells; however, the magnitude of the enhanced release is small when compared to the differences in MMP-2 release in cells from preeclamptic and normal pregnancies. Furthermore, TIMP-1 and -2 release is not affected by changes in oxygen. It is unlikely that oxygen is a key mediator of the enhanced MMP-2, TIMP-1 and TIMP-2 release observed in preeclamptic cells.

The role of vascular endothelial growth factor (VEGF) during peritoneal dissemination of ovarian carcinoma and the association with tumor microvessel density (MVD) and matrix metalloproteinase (MMP) activity was investigated. To this end, MVD, tumor tissue and ascitic fluid levels of VEGF, and MMP activity of ascitic fluid were examined in patients with ovarian cancer and benign ovarian tumor. The effect of ascites on cell growth, cell invasion activity and angiogenesis was investigated in vitro. Ascitic fluid and tumor tissue samples were obtained from 15 patients with benign ovarian tumor and 24 patients with ovarian carcinoma. Tissue extract and ascitic fluid levels of VEGF were measured using enzyme immunoassay. Tumor microvessels were detected immunohistochemically. MMP activity was measured by gelatin zymography. For the in vitro experiment, the SKOV-3 human ovarian carcinoma cell line was utilized. Cell growth was examined using MTT-assay, cell invasion activity was measured by Matrigel in vitro invasion assay, and neovascularization was assessed using an angiogenesis kit. VEGF levels in tissue extract and ascitic fluid, MVD, expression of active form MMP-2 in ascitic fluid and ascites volume were higher in ovarian cancer patients than in benign ovarian tumor patients. In addition, these were elevated in stage III and IV diseases compared to stage I and II diseases in ovarian cancer patients. MVD and expression of active form MMP-2 in ascitic fluid were closely correlated with VEGF level in tissue extracts, and MVD and ascites volume were closely correlated with VEGF level in ascitic fluid. Cell invasive activity and angiogenesis activity increased when cells were exposed to ascites. These increases were apparent when exposed to ascites obtained from ovarian cancer patients and were related to VEGF concentrations of ascitic fluid and expression of active form MMP-2 in ascitic fluid. The increased VEGF secreted from tumor cells is suggested to enhance tumor growth through angiogenesis, to produce ascites and to elevate ascitic VEGF concentrations and expression of active form MMP-2. The progression of peritoneal involvement may be induced by elevated VEGF and expression of active form MMP-2, followed by increased VEGF in the primary tumor. Control of VEGF in the primary tumor may become an effective strategy against peritoneal dissemination of ovarian carcinoma.

A 26-year-old woman with neurofibromatosis 1 was admitted to our hospital for investigation of prolonged hypertension after toxemia of pregnancy. Plasma renin activity was elevated. From the renogram, stenosis of right renal artery was suspected and we performed renal arteriography, which revealed proximal right renal artery stenosis. The intravascular ultrasound (IVUS) image showed concentric stenosis with intimal and medial hypertrophy, which was iso-echoic and partly high echoic. Percutaneous transluminal renal angioplasty was performed and the lesion was well dilated. After angioplasty, blood pressure normalized in a week. From the clinical course and the IVUS image, we suspected that renal artery stenosis was due to neurofibromatosis 1.

Objective: We have recently demonstrated that matrix metalloproteinase-2 (MMP-2) alters vascular function through cleavage of vasoactive peptides, resulting in increased vasoconstriction and reduced vasodilation. We, therefore, hypothesized that MMP levels are increased in women with preeclampsia. In addition, because vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of preeclampsia and is involved in angiogenesis that requires the release of proteases to allow for migration of endothelial cells, we hypothesized that VEGF increases release of MMPs from endothelial cells., Methods: We used zymographic analysis to evaluate MMP-2/MMP-9 levels in plasma of women with preeclampsia (n=12) compared to women with uncomplicated pregnancies (n=12). In addition, we evaluated the changes in the levels of MMP-2 and MMP-9 as well as tissue inhibitors of MMPs (TIMP-1 and TIMP-2) released by cultured human umbilical vein endothelial cells in response to VEGF (0.1-10 ng/mL)., Results: Our data showed that plasma MMP-2 levels were significantly higher in women with preeclampsia compared to women with uncomplicated pregnancies (arbitrary intensity units: 690 +/-111 and 252 +/-56, respectively, p<0.05). MMP-9 levels were below the level of detection. In addition, VEGF stimulated endothelial MMP-2 and MMP-9 release in a concentration- and time-dependent (6-24 h) manner. Moreover, VEGF stimulation of MMP release occurs without significantly affecting the release of TIMP-1 and TIMP-2., Conclusions: These data suggest that VEGF promotes secretion of MMPs from endothelial cells that, in turn, could alter vascular function in women with preeclampsia.