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To assess whether there are temporal differences altering the clinical outcomes of severe trauma patients in Japan. This was a retrospective cohort study that used recorded data from the Japan Trauma Data Bank. Severe trauma patients who had an injury severity score of greater than 16 were included. The hospital arrival time was categorized into daytime (8 a.m.–7:59 p.m.) and nighttime (8 p.m.–7:59 a.m.). The hospital arrival day of the week was categorized into business days and non-business days. The primary outcome was in-hospital mortality. A total of 65,136 severe trauma patients were analyzed. In-hospital mortality was 15.6% in the daytime and 14.4% in the nighttime, and 15.5%, and 14.6% on business days and non-business days, respectively. Nighttime was associated with decreased in-hospital mortality compared to daytime (odds ratio = 0.817, 95% confidence interval = 0.764–0.874) and a non-business day was not associated with in-hospital mortality. We did not find a negative off-hour effect on in-hospital mortality among severe trauma patients.

EndoVascular and Hybrid Trauma Management (EVTM) has been recently introduced in the treatment of severe pelvic ring injuries. This multimodal method of hemorrhage management counts on several strategies such as the REBOA (resuscitative endovascular balloon occlusion of the aorta). Few data exist on the use of REBOA in patients with a severely injured pelvic ring. The ABO (aortic balloon occlusion) Trauma Registry is designed to capture data for all trauma patients in hemorrhagic shock where management includes REBOA placement. Among all patients included in the ABO registry, 72 patients presented with severe pelvic injuries and were the population under exam. 66.7% were male. Mean and median ISS were respectively 43 and 41 (SD ± 13). Isolated pelvic injuries were observed in 12 patients (16.7%). Blunt trauma occurred in 68 patients (94.4%), penetrating in 2 (2.8%) and combined in 2 (2.8%). Type of injury: fall from height in 15 patients (23.1%), traffic accident in 49 patients (75.4%), and unspecified impact in 1 patient (1.5%). Femoral access was gained pre-hospital in 1 patient, in emergency room in 43, in operating room in 12 and in angio-suite in 16. REBOA was positioned in zone 1 in 59 patients (81,9%), in zone 2 in 1 (1,4%) and in zone 3 in 12 (16,7%). Aortic occlusion was partial/periodical in 35 patients (48,6%) and total occlusion in 37 patients (51,4%). REBOA associated morbidity rate: 11.1%. Overall mortality rate was 54.2% and early mortality rate (≤ 24 h) was 44.4%. In the univariate analysis, factors related to early mortality (≤ 24 h) are lower pH values (p = 0.03), higher base deficit (p = 0.021), longer INR (p = 0.012), minor increase in systolic blood pressure after the REBOA inflation (p = 0.03) and total aortic occlusion (p = 0.008). None of these values resulted significant in the multivariate analysis. In severe hemodynamically unstable pelvic trauma management, REBOA is a viable option when utilized in experienced centers as a bridge to other treatments; its use might be, however, accompanied with severe-to-lethal complications.

Background Numerous patients who receive hemodialysis (HD) undergo total knee arthroplasty (TKA) due to advanced knee joint arthritis. However, there are few studies that describe the clinical outcomes and complications of TKA in HD patients. This study investigated the mid-term results of TKA in patients undergoing HD. Methods This single-center retrospective study compared clinical and surgical outcomes following TKA in patients who were receiving HD with those who were not. We used propensity scores to match 21 knees of 18 patients who received HD to 706 knees of 569 patients who had not received HD, from a total of 727 knees (587 patients) that underwent primary unilateral TKA. The clinical outcomes were evaluated using the American Knee Society Score-knee (AKSS-knee) and AKSS-function scores. The primary surgical outcome measure was the number of knees with postoperative complications. Results In both the HD and non-HD groups, postoperative AKSS-knee and function scores significantly improved when compared to preoperative values. Postoperative AKSS-knee and function scores were not significantly different between the groups. The number of knees with postoperative complications was larger in the HD group than the non-HD group within the first postoperative month, 0–12 months, 12–24 months, 0–24 months, and two years after surgery. Additionally, in the HD group, more complications occurred in the first month than any subsequent month in the two years after surgery. Conclusions TKA improves AKSS-knee and function scores equivalently for HD patients and non-HD patients. However, HD patients develop more complications after TKA, especially within the first month. Therefore, surgeons who perform TKA for HD patients should obtain informed consent after explaining the possible complications, and HD patients should be carefully observed following TKA.

Purpose Hospital services are reduced during off-hour such as nighttime or weekend. Investigations of the off-hour effect on initial management and outcomes in sepsis are very limited. Thus, we tested the hypothesis that patients who were diagnosed with severe sepsis during the nighttime or on non-business days had altered initial management and clinical outcomes. Materials and methods Patients with severe sepsis from 59 ICUs between 2016 and 2017 were enrolled. The patients were categorized according to the diagnosis time or day and were then compared. The primary outcome was in-hospital mortality. Results One thousand one hundred and forty-eight patients were analyzed; 769 daytime patients, vs. 379 nighttime patients, and 791 business day patients vs. 357 non-business day patients. There were no significant differences in in-hospital mortality between either daytime and nighttime (24.4% vs. 21.4%, P = .27; nighttime, adjusted odds ratio [OR] 1.17, 95% confidence interval [CI], 0.87–1.59, P = .30) or between business and non-business days (22.9% vs. 24.6%, P = .55; non-business day, adjusted OR 0.85, 95% CI 0.60–1.22, P = .85). Time to antibiotics was significantly shorter in the nighttime (114 vs. 89 min, P = .0055). Conclusions Nighttime and weekends were not associated with increased in-hospital mortality of severe sepsis.

Aim Effective courses are essential for highly invasive procedures such as resuscitative endovascular balloon occlusion of the aorta. However, the coronavirus disease pandemic has forced the postponement of on‐site educational courses due to transmission concerns. Few studies have examined the effectiveness of Web‐based education in highly invasive procedures. To address this knowledge gap, this study aimed to investigate whether knowledge acquisition and confidence after the Web‐based course are different from those acquired after the on‐site course, using pre‐ and postcourse test scores. Methods The increase in scores before and after the course was compared between the on‐site and Web‐based courses. The questions reflected knowledge about seven different topics in the course modules. In addition, participants were asked about their self‐rated confidence about three topics before and after the course. Results Thirty learners completed the on‐site course, and 21 learners completed the Web‐based course. Forty‐seven learners completed both the precourse and postcourse tests. In both courses, the difference between the precourse and postcourse test scores showed a statistically significant increase in knowledge (on‐site course: increased score, 1.8; 95% confidence interval, 0.8 to 2.8; Web‐based course: increased score, 1.6, 95% confidence interval, 0.5 to 2.5). However, the difference was not statistically significant in the self‐rated confidence scores about “sheath and catheter removal” among learners of the Web‐based course. Conclusion Knowledge increased significantly in both the on‐site and Web‐based courses. However, the Web‐based course might not be sufficient to give learners confidence in the procedures., Few studies have examined the effectiveness of Web‐based education in highly invasive procedures. In both on‐site and Web‐based courses, the difference between the precourse and postcourse test scores showed a statistically significant increase in knowledge; however, the difference was not statistically significant in the self‐rated confidence scores. Although knowledge increased significantly in both the on‐site and Web‐based course, the Web‐based course might not be sufficient to give learners confidence during the procedures.

Contains fulltext : 215819.pdf (Publisher’s version ) (Open Access) Renal and urogenital injuries occur in approximately 10-20% of abdominal trauma in adults and children. Optimal management should take into consideration the anatomic injury, the hemodynamic status, and the associated injuries. The management of urogenital trauma aims to restore homeostasis and normal physiology especially in pediatric patients where non-operative management is considered the gold standard. As with all traumatic conditions, the management of urogenital trauma should be multidisciplinary including urologists, interventional radiologists, and trauma surgeons, as well as emergency and ICU physicians. The aim of this paper is to present the World Society of Emergency Surgery (WSES) and the American Association for the Surgery of Trauma (AAST) kidney and urogenital trauma management guidelines.

IntroductionResuscitation using blood products is critical during the acute postinjury period. However, the optimal target haemoglobin (Hb) levels have not been adequately investigated. With the restrictive transfusion strategy for critically injured patients (RESTRIC) trial, we aim to compare the restrictive and liberal red blood cell (RBC) transfusion strategies.Methods and analysisThis is a cluster-randomised, crossover, non-inferiority trial of patients with severe trauma at 22 hospitals that have been randomised in a 1:1 ratio based on the use of a restrictive or liberal transfusion strategy with target Hb levels of 70–90 or 100–120 g/L, respectively, during the first year. Subsequently, after 1-month washout period, another transfusion strategy will be applied for an additional year. RBC transfusion requirements are usually unclear on arrival at the emergency department. Therefore, patients with severe bleeding, which could lead to haemorrhagic shock, will be included in the trial based on the attending physician’s judgement. Each RBC transfusion strategy will be applied until 7 days postadmission to the hospital or discharge from the intensive care unit. The outcomes measured will include the 28-day survival rate after arrival at the emergency department (primary), the cumulative amount of blood transfused, event-free days and frequency of transfusion-associated lung injury and organ failure (secondary). Demonstration of the non-inferiority of restrictive transfusion will emphasise its clinical advantages.Ethics and disseminationThe trial will be performed according to the Japanese and International Ethical guidelines. It has been approved by the Ethics Committee of each participating hospital and The Japanese Association for the Surgery of Trauma (JAST). Written informed consent will be obtained from all patients or their representatives. The results of the trial will be disseminated to the participating hospitals and board-certified educational institutions of JAST, submitted to peer-reviewed journals for publication, and presented at congresses.Trial registration numberUMIN Clinical Trials Registry; UMIN000034405. Registered 8 October 2018.

Background The outcomes of multiple injury patients with concomitant torso hemorrhage and traumatic brain injury (TBI) are very poor. The hybrid emergency room system (HERS) is a trauma management system designed to complete resuscitation, computed tomography (CT), surgery, angioembolization, and intracranial pressure (ICP) monitoring all in one trauma resuscitation room without patient transfer. We aimed to review the outcomes of polytrauma patients who underwent concurrent bleeding control and ICP monitoring using the HERS. Methods In this retrospective observational study, we enrolled patients who underwent concurrent bleeding control and ICP monitoring using the HERS between August 2011 and June 2018. Initial data on vital signs, Injury Severity Score (ISS), probability of survival (Ps) calculated by the Trauma and Injury Severity Score (TRISS), intervention type, 28-day mortality, and Extended Glasgow Outcome Scale at 6 months after injury were collected. Continuous variables were expressed as the median (25th and 75th percentiles) and categorical variables as numbers (%). Results Ten patients were included in the analysis. The injury severity of the patients was as high as an ISS of 58 (50–64) and TRISS Ps of 0.15 (0.02–0.36). Seven of the 10 (70%) patients had hemodynamic instability within 30 min from arrival. The recorded durations from arrival to events were CT examination 9 (6–16) min, bleeding control procedure 29 (22–42) min, and neurosurgical intervention 39 (31–53) min. Four of the 10 patients (40%) survived to discharge, and two of them (20%) were able to live independently at 6 months after injury. Conclusions The concurrent performance of bleeding control procedure and ICP monitoring would be feasible in HERS settings among polytrauma patients with exsanguinating hemorrhage and TBI. Electronic supplementary material The online version of this article (10.1186/s13017-018-0218-x) contains supplementary material, which is available to authorized users.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable alternative to resuscitative thoracotomy (RT) in refractory hemorrhagic patients. We evaluated REBOA strategies using Japanese multi-institutional data.The DIRECT-IABO investigators registered trauma patients requiring REBOA from 18 hospitals. Patients' characteristics, outcomes, and time in initial treatment were collected and analyzed.From August 2011 to December 2015, 106 trauma patients were analyzed. The majority of patients were men (67%) (median BMI of 22 kg/m, 96% blunt injured). REBOA occurred in the field (1.9%, all survived30 days), emergency department (75%), angiography suite (17%), and operating room (1.9%). Initial deployment was at zone I in 93% and partial occlusion in 70% of cases. RT and REBOA were combined in 30 patients (RT+REBOA group) who showed significantly higher injury severity score (44 vs. 36, P=0.001) and chest abbreviated injury scale (4 vs. 3; P0.001) than the REBOA-alone group (n=76). Frequent cardiopulmonary resuscitation (73%), longer prothrombin time-international normalised ratio, lower pH, and higher lactate were observed in the RT+REBOA. Among 24 h nonsurvivors (n=30) of the REBOA alone, preocclusion systolic blood pressure was lower (43 vs. 72 mmHg; P=0.002), indicating impending cardiac arrest, and duration of occlusion was longer (60 vs. 31 min; P=0.010). In the RT+REBOA (n=30), six survived beyond 24 h, three beyond 30 days, and achieved survival discharge.Partial occlusion was performed in 70% of patients. Undelayed deployment of REBOA without presenting impending cardiac arrest with shorter balloon occlusion (30 min at zone I with partial occlusion) might be related to successful hemodynamic stabilization and improved survival. Further evaluation should be performed prospectively.

BACKGROUND Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable resuscitation approach for a subdiaphragmatic injury that can regulate arterial blood flow. On the other hand, the evaluation of venous or portal venous blood flow during REBOA remains insufficient because invasive cannulation or exposure of the vessel may affect the blood flow, and Doppler echography is highly operator-dependent. However, phase contrast magnetic resonance imaging has enabled accurate evaluation and noninvasive measurement. This study aimed to investigate the change of venous and portal venous blood flow during REBOA in a porcine model. METHODS Seven pigs were anesthetized, and a REBOA catheter was placed. The blood flows of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV), and superior vena cava (SVC) were measured using phase contrast magnetic resonance imaging, in both the balloon deflated (no-REBOA) and fully balloon inflated (REBOA) states. Mean arterial pressure (MAP), central venous pressure, cardiac index, and systemic vascular resistance index were measured. RESULTS The blood flows of the suprahepatic, infrahepatic, and distal IVC, HV, and PV in the no-REBOA state were 1.40 ± 0.36 L·min, 0.94 ± 0.16 L·min, 0.50 ± 0.19 L·min, 0.060 ± 0.018 L·min, and 0.32 ± 0.091 L·min, respectively. The blood flow of each section in the REBOA condition was significantly decreased at 0.41 ± 0.078 (33% of baseline), 0.15 ± 0.13 (15%), 0.043 ± 0.034 (9%), 0.029 ± 0.017 (37%), and 0.070 ± 0.034 L·min (21%), respectively. The blood flow of the SVC increased significantly in the REBOA condition (1.4 ± 0.63 L·min vs. 0.53 ± 0.14 L·min [257%]). Mean arterial pressure, central venous pressure, cardiac index, and systemic vascular resistance index were significantly increased after REBOA inflation. CONCLUSION Resuscitative endovascular balloon occlusion of the aorta decreased blood flows of the IVC, HV, and PV and increased blood flow of the SVC. This result could be explained by the collateral flow from the lower body to the SVC. A better understanding of the effect of REBOA on the venous and portal venous systems may help control liver injury.

Introduction Partial resuscitative endovascular balloon occlusion of the aorta (P-REBOA) is a modified REBOA technique designed to help ameliorate ischemia-reperfusion injury. The balloon is partially deflated, allowing a proportion of aortic flow distal to the balloon. The aim of this study is to use an ovine model of haemorrhagic shock to correlate the degree of occlusion to several hemodynamic indices. Materials and methods Six sheep weighing 35–46 kg underwent a controlled venous haemorrhage inside a CT scanner until the systolic arterial pressure (AP) dropped to Results A diameter of the aorta at zone I was 16.0 (15.7–17.2) mm, with a cross-sectional area of 212 (194–233) mm2. Median volume of saline injected into the balloon until total occlusion was 7.0 (6.3–8.5) mL. During gradual balloon inflation, proximal MAP increased and distal MAP decreased proportionate to the degree of occlusion, in a linear fashion (proximal: r2 = 0.85, p Conclusion Serial CT angiography at an ovine model of haemorrhagic shock demonstrates a correlation between the femoral MAP, F/C pressure gradient and degree of zone I P-REBOA during the staged partial aortic occlusion. These parameters should be considered potential parameters to define the degree of P-REBOA during animal research and clinical practice.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) performed by emergency physicians has been gaining acceptance as a less invasive technique than resuscitative thoracotomy.To evaluate access-related complications and duration of occlusions during REBOA.Patients with haemorrhagic shock requiring REBOA, from 18 hospitals in Japan, included in the DIRECT-IABO Registry were studied. REBOA-related characteristics were compared between non-survivors and survivors at 24 hours. 24-Hour survivors were categorised into groups with small (≤8 Fr), large (≥9 Fr) or unusual sheaths (oversized or multiple) to assess the relationship between the sheath size and complications. Haemodynamic response, occlusion duration and outcomes were compared between groups with partial and complete REBOA.Between August 2011 and December 2015, 142 adults undergoing REBOA were analysed. REBOA procedures were predominantly (94%) performed by emergency medicine (EM) physicians. The median duration of the small sheath (n=53) was 19 hours compared with 7.5 hours for the larger sheaths (P=0.025). Smaller sheaths were more likely to be removed using external manual compression (96% vs 45%, P0.001). One case of a common femoral artery thrombus (large group) and two cases of amputation (unusual group) were identified. Partial REBOA was carried out in more cases (n=78) and resulted in a better haemodynamic response than complete REBOA (improvement in haemodynamics, 92% vs 70%, P=0.004; achievement of stability, 78% vs 51%, P=0.007) and allowed longer occlusion duration (median 58 vs 33 min, P=0.041). No statistically significant difference in 24-hour or 30-day survival was found between partial and complete REBOA.In Japan, EM physicians undertake the majority of REBOA procedures. Smaller sheaths appear to have fewer complications despite relatively prolonged placement and require external compression on removal. Although REBOA is a rarely performed procedure, partial REBOA, which may extend the occlusion duration without a reduction in survival, is used more commonly in Japan.

Trauma pan-scan (TPS) offers a benefit in trauma care. Resuscitative endovascular resuscitative endovascular occlusion of the aorta (REBOA) may allow the opportunity to scan hemodynamically unstable (HU) polytrauma patients; however, the benefits and risks of REBOA-TPS remains unknown. The rationale for TPS in HU patients is to choose the best disposition and to quickly achieve hemostasis rather than directly initiating surgery without scanning. TPS would most benefit geriatric trauma patients and those with coagulopathies with unidentified bleeding sources, particularly non-cavitary hemorrhage in blunt trauma and accompanying brain injury, because TPS may predict unexpected physiological collapse by anatomical imaging. CT is a common cause of flow disruption, but trauma team training shortened the time spent in the CT room from 16.8 to 7.3 minutes (P

Patients receiving extracorporeal membrane oxygenation (ECMO) often require continuous renal replacement therapy (CRRT). The intra-circuit pressure of adult ECMO usually deviates from the physiological range. We investigated the use of CRRT connected to an ECMO circuit with physiological intra-circuit pressures (0–150 mmHg, defined as the “safety range”) using an in vitro experiment involving a water-filled ECMO circuit. The intra-circuit pressure pre-pump, post-pump, and post-oxygenator were measured while varying the height of the pump or ECMO flow. The bypass conduit pressure and distance from the post-oxygenator port were measured to find the “safety point”, where the bypass pressure remained within the safety range. Both drainage and return limbs of the CRRT machine were connected to the safety point and the inlet and outlet pressures of the hemofilter were recorded while varying the ECMO and CRRT flow. The pre-pump pressure only remained within the safety range for heights >75 cm (ECMO flow = 4 L/min) or ECMO flow

Aim To investigate the clinical utility of interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) as predictive markers in consideration of the time-course changes in critically ill patients with organ dysfunction. Methods Serum levels of IL-6, PCT, CRP, and Sequential Organ Failure Assessment (SOFA) scores were measured sequentially in 92 patients during their initial 5 days following admission to the intensive care unit. Maximum values were analyzed. Patients were assigned to a low ( ≤ 8), intermediate ( > 8 and ≤ 16), or high ( > 16 and ≤ 24) SOFA score group. Results There were significant differences in the maximum serum levels of IL-6 and PCT among the three SOFA score groups (IL-6, P < 0.0001; PCT, P = 0.0004). Specifically, comparisons between the groups revealed significant differences in IL-6 levels (low versus intermediate, P = 0.0007; intermediate versus high, P = 0.0010). The probability of patients with the maximum value was greatest on day 1 (56.5%) for IL-6, on day 1 (39.1%) or day 2 (38.0%) for PCT, on day 3 (39.1%) for CRP, and on day 1 (43.5%) for SOFA score. The median (interquartile range) peak day of IL-6 was day 1 (1–2), which was significantly earlier than that of SOFA score at day 2 (1–3) (P = 0.018). Conclusion Serum levels of IL-6 reflected the severity of organ dysfunction in critically ill patients most accurately compared to PCT and CRP. Interleukin-6 elevated soonest from the insult and reached its peak earlier than SOFA score.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) increases proximal pressure, and simultaneously induces distal ischemia. We aimed to evaluate organ ischemia during partial REBOA (P-REBOA) with computed tomography (CT) perfusion in a swine model. The maximum balloon volume was recorded as total REBOA when the distal pulse pressure ceased. The animals (n = 4) were scanned at each 20% of the maximum balloon volume, and time-density curve (TDC) were analysed at the aorta, portal vein (PV), liver parenchyma, and superior mesenteric vein (SMV, indicating mesenteric perfusion). The area under the TDC (AUTDC), the time to peak (TTP), and four-dimensional volume-rendering images (4D-VR) were evaluated. The TDC of the both upper and lower aorta showed an increased peak and delayed TTP. The TDC of the PV, liver, and SMV showed a decreased peak and delayed TTP. The dynamic 4D-CT analysis suggested that organ perfusion changes according to balloon volume. The AUTDC at the PV, liver, and SMV decreased linearly with balloon inflation percentage to the maximum volume. 4D-VR demonstrated the delay of the washout in the aorta and retrograde flow at the inferior vena cava in the highly occluded status.

The concept of EndoVascular resuscitation and Trauma Management (EVTM) has recently been proposed to refer to the use of endovascular techniques for resuscitation, haemorrhage control, and definitive trauma management. Although the popularity of resuscitative endovascular balloon occlusion of the aorta (REBOA) has been growing, the use of the EVTM or CT imaging is still limited in hemodynamically unstable patients. To overcome the current limitations, the Hybrid Emergency Room System (HERS) was introduced in 2011. HERS consists of an operating table with an angiographic C-arm and a sliding CT scanner system in the resuscitation area, which allows all emergency diagnostic and therapeutic interventions without relocating the patient. This paper deals with current limitations of EVTM and proposes solutions with HERS. In the HERS environment, patients can undergo IR in the resuscitation room, which may expand the indications of IR to include hemodynamically unstable patients. HERS can also reduce CT scanning time to identify unexpected injuries or traumatic brain injury. It also allows prompt neurosurgical intervention simultaneously with haemorrhage control. REBOA is a viable adjunct treatment for refractory haemorrhagic shock but its procedure-related complications must be considered. REBOA can be performed more safely, rapidly, and accurately in HERS, followed by immediate definitive haemostasis. In addition, HERS may safely extend the application of REBOA-CT to identify accurate injury site. HERS may be an ideal EVTM solution for the trinity of surgery, endovascular treatment, and imaging in trauma care. We will continue to explore the most radical and safest EVTM in the HERS environment.

Backgroud: Angioembolization is a widely accepted method for an effective and useful hemostasis procedure in pelvic fracture (PF) patients. We evaluated and introduce the time course of the initial management and angiography in HU pelvic fracture patients. Methods: We retrospectively reviewed 56 PF patients who underwent IR from May 2010 to Dec 2016. We defined arrival to angiographytime (ATAT), it was recorded in all enrolled patients in which the first angiography image represented the initiation of angiography. We also evaluated total embolization time (TET) and single artery embolization time (SAET; time for artery selection, injection, embolization, and confirmation). Results: The median ATAT and TET was respectively 73 and 33 minutes. They were much faster than the previous reports. Conclusions: Our trauma IR strategy with specialized team might contribute to shorten the management time.

Background Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) may improve Systolic Blood Pressure (SBP) in hypovolemic shock. It has, however, not been studied in patients with impending traumatic cardiac arrest (ITCA). We aimed to study the feasibility and clinical outcome of REBOA in patients with ITCA using data from the ABOTrauma Registry. Methods Retrospective and prospective data on the use of REBOA from 16 centers globally were collected. SBP was measured both at pre- and post-REBOA inflation. Data collected included patients' demography, vascular access technique, number of attempts, catheter size, operator, zone and duration of occlusion, and clinical outcome. Results There were 74 patients in this high-risk patient group. REBOA was performed on all patients. A 7-10Fr catheter was used in 66.7% and 58.5% were placed on the first attempt, 52.1% through blind insertion and 93.2% inflated in Zone I, 64.8% for a period of 30 to 60 min, 82.1% by ER doctors, trauma surgeons, or vascular surgeons. SBP significantly improved to 90 mm Hg following the inflation of REBOA. 36.6% of the patients survived. Conclusions Our study has shown that REBOA may be performed in patients with ITCA, SBP can be elevated, and 36.6% of the patients survived if REBOA placement is successful.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines., other authors: Satoru Hashimoto,Daisuke Hasegawa,Junji Hatakeyama,Naoki Hara,Naoki Higashibeppu,Nana Furushima,Hirotaka Furusono,Yujiro Matsuishi,Tasuku Matsuyama,Yusuke Minematsu,Ryoichi Miyashita,Yuji Miyatake,Megumi Moriyasu,Toru Yamada,Hiroyuki Yamada,Ryo Yamamoto,Takeshi Yoshida,Yuhei Yoshida,Jumpei Yoshimura,Ryuichi Yotsumoto,Hiroshi Yonekura,Takeshi Wada,Eizo Watanabe,Makoto Aoki,Hideki Asai,Takakuni Abe,Yutaka Igarashi,Naoya Iguchi,Masami Ishikawa,Go Ishimaru,Shutaro Isokawa,Ryuta Itakura,Hisashi Imahase,Haruki Imura,Takashi Irinoda,Kenji Uehara,Noritaka Ushio,Takeshi Umegaki,Yuko Egawa,Yuki Enomoto,Kohei Ota,Yoshifumi Ohchi,Takanori Ohno,Hiroyuki Ohbe,Kazuyuki Oka,Nobunaga Okada,Yohei Okada,Hiromu Okano,Jun Okamoto,Hiroshi Okuda,Takayuki Ogura,Yu Onodera,Yuhta Oyama,Motoshi Kainuma,Eisuke Kako,Masahiro Kashiura,Hiromi Kato,Akihiro Kanaya,Tadashi Kaneko,Keita Kanehata,Ken-ichi Kano,Hiroyuki Kawano,Kazuya Kikutani,Hitoshi Kikuchi,Takahiro Kido,Sho Kimura,Hiroyuki Koami,Daisuke Kobashi,Iwao Saiki,Masahito Sakai,Ayaka Sakamoto,Tetsuya Sato,Yasuhiro Shiga,Manabu Shimoto,Shinya Shimoyama,Tomohisa Shoko,Yoh Sugawara,Atsunori Sugita,Satoshi Suzuki,Yuji Suzuki,Tomohiro Suhara,Kenji Sonota,Shuhei Takauji,Kohei Takashima,Sho Takahashi,Yoko Takahashi,Jun Takeshita,Yuuki Tanaka,Akihito Tampo,Taichiro Tsunoyama,Kenichi Tetsuhara,Kentaro Tokunaga,Yoshihiro Tomioka,Kentaro Tomita,Naoki Tominaga,Mitsunobu Toyosaki,Yukitoshi Toyoda,Hiromichi Naito,Isao Nagata,Tadashi Nagato,Yoshimi Nakamura,Yuki Nakamori,Isao Nahara,Hiromu Naraba,Chihiro Narita,Norihiro Nishioka,Tomoya Nishimura,Kei Nishiyama,Tomohisa Nomura,Taiki Haga,Yoshihiro Hagiwara,Katsuhiko Hashimoto,Takeshi Hatachi,Toshiaki Hamasaki,Takuya Hayashi,Minoru Hayashi,Atsuki Hayamizu,Go Haraguchi,Yohei Hirano,Ryo Fujii,Motoki Fujita,Naoyuki Fujimura,Hiraku Funakoshi,Masahito Horiguchi,Jun Maki,Naohisa Masunaga,Yosuke Matsumura,Takuya Mayumi,Keisuke Minami,Yuya Miyazaki,Kazuyuki Miyamoto,Teppei Murata,Machi Yanai,Takao Yano,Kohei Yamada,Naoki Yamada,Tomonori Yamamoto,Shodai Yoshihiro,Hiroshi Tanaka,Osamu Nishida, Guidelines

The techniques of diagnostic and interventional radiology (IR) have recently shown significant efficacy in trauma care along when combined with surgical procedures. A multifaceted approach to traffic accidents has reduced the number of trauma patients in Japan, which has necessitated simulation education to provide practical experience and ensure proficiency. The objective of this paper is to report the educational development of endovascular and hybrid workshop in Japan. The Japanese Society of Diagnostic and Interventional Radiology in Emergency, Critical care, and Trauma (DIRECT) was established in 2011 to maximize the benefit of diagnostic and interventional radiology in emergency or trauma settings. DIRECT conducts trauma endovascular workshop for emergency medicine physician, acute care surgeons and IR physicians. From July 2011 to June 2016, DIRECT has conducted 14 simulator workshops, six endovascular workshops using a porcine model, and four hybrid trauma management workshops, of which the two were conducted with porcine. The simulation workshop designed for novice learners and included Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) deployment using a pressurized silicone model, catheter and guidewire manipulation using a three-dimensional (3D) vessel silicone model and virtual fluoroscopic simulator, and metallic coil deployment. Porcine simulations for intermediate-level physicians were conducted and endovascular tools included different occlusion materials. In the hybrid strategy model in using a porcine model of injury, the participants combined both surgical and endovascular procedures such as REBOA, selective balloon occlusion, and N-butyl cyanoacrylate embolization. DIRECT is a vital bridge between emergency/trauma and IR and workshops are essential for improved trauma care.

Aim Multiple lines and tubes often complicate bed transfer in critically ill patients. To solve this problem, the authors developed medical equipment attached to a transfer board (“transfer board tree”) that integrates the patient, transfer board, and medical equipment. The objective of this study was to evaluate the efficiency and safety of the transfer board tree. Methods Forty mechanically ventilated patients (20 transfer board tree, 20 conventional) in the intensive care unit who were transported for computed tomography were enrolled. Transfer times and adverse events were recorded. Results Transfer board tree patients had significantly shorter transfer times. There were two adverse events only in the conventional group. Conclusions The transfer board tree enables rapid intrahospital transport of intensive care patients with sufficient monitoring.

Aim To assess the clinical benefits of introducing a medical emergency team system for early medical intervention in hospital care. Methods This prospective analysis included all cases of medical emergency team activation during the first year after the introduction of the medical emergency team system at Chiba University Hospital (Chiba, Japan) in February 2011. The rates of in-hospital mortality and unexpected events before and after introduction of the medical emergency team system were compared. Results The total number of medical emergency team activation calls was 83 (4.9 per 1,000 admissions). The activation of the medical emergency team system was requested most frequently from the general ward (56.6%) and by a physician (57.8%), with the most important reasons for activation being cardiac arrest (37.3%), breathing abnormality (33.7%), and impaired consciousness (32.5%). The most frequent medical interventions by the medical emergency team were intubation (43.3%) and oxygen inhalation (41.0%). Approximately one-half of the patients requiring activation of the medical emergency team system were critically ill and needed subsequent intensive care unit admission. Although no significant difference was observed between the pre- and post- medical emergency team in-hospital mortalities (2.1% versus 2.0%, respectively), the incidence rate of serious events significantly decreased (12.4% versus 6.8%, respectively; P = 0.015). Conclusion Most patients requiring activation of the medical emergency team system were critically ill and needed emergency treatment at the location of the medical emergency team activation, with subsequent critical care. Although the introduction of the medical emergency team system did not affect the in-hospital mortality rate, it reduced the incidence of unexpected serious adverse events, suggesting that it may be clinically useful.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is now a feasible and less invasive resuscitation procedure. This study aimed to compare the clinical course of trauma and non-trauma patients undergoing REBOA. Patient demographics, etiology, bleeding sites, hemodynamic response, length of critical care, and cause of death were recorded. Characteristics and outcomes were compared between non-trauma and trauma patients. Kaplan–Meier survival analysis was then conducted. Between August 2011 and December 2015, 142 (36 non-trauma; 106 trauma) cases were analyzed. Non-traumatic etiologies included gastrointestinal bleeding, obstetrics and gynecology-derived events, visceral aneurysm, abdominal aortic aneurysm, and post-abdominal surgery. The abdomen was a common bleeding site (69%), followed by the pelvis or extra-pelvic retroperitoneum. None of the non-trauma patients had multiple bleeding sites, whereas 45% of trauma patients did (P

Purpose: Although vancomycin (VCM) is not absorbed from healthy intestinal mucosa, elevations in the serum VCM concentrations have been reported in some cases. The aims of this study are to evaluate the necessity of therapeutic drug monitoring (TDM) during enteral VCM administration in critically ill patients. Materials and Methods: In this retrospective study, we enrolled 19 patients admitted to our intensive care unit who were treated with enteral VCM from December 2006 to January 2014. Clinical factors were compared between two groups: Group E whose serum concentrations were detectable, and Group N whose concentrations were below the detection limit of the VCM assay. Results: Group E comprises seven patients and group N comprises twelve patients. The fasting duration in Group E was significantly longer compared with that in Group N (17 vs. 8 days, p = 0.023). Furthermore, there was a significant correlation between the serum VCM concentrations and the fasting duration (r=0.79, p

Background A sudden shortage of physician resources due to overwhelming patient needs can affect the quality of care in the emergency department (ED). Developing effective response strategies remains a challenging research area. We created a novel system using information and communication technology (ICT) to respond to a sudden shortage, and tested the system to determine whether it would compensate for a shortage. Methods Patients (n = 4890) transferred to a level I trauma center in Japan during 2012–2015 were studied. We assessed whether the system secured the necessary physicians without using other means such as phone or pager, and calculated fulfillment rate by the system as a primary outcome variable. We tested for the difference in probability of multiple casualties among total casualties transferred to the ED as an indicator of ability to respond to excessive patient needs, in a secondary analysis before and after system introduction. Results The system was activated 24 times (stand-by request [n = 12], attendance request [n = 12]) in 24 months, and secured the necessary physicians without using other means; fulfillment rate was 100%. There was no significant difference in the probability of multiple casualties during daytime weekdays hours before and after system introduction, while the probability of multiple casualties during night or weekend hours after system introduction significantly increased compared to before system introduction (4.8% vs. 12.9%, P

Dielectric laser accelerators (DLAs) have great potential for applications, since they can generate acceleration gradients in the range of GeV/m and produce attosecond electron bunches. We described a novel reverse dual-grating dielectric accelerator structure made up of Silicon which is expected to improve beam confinement, and make fabrication easier. Numerical simulation results show that this structure effectively manipulates the laser field and generates a standing wave in the vacuum channel with a phase velocity synchronized to relativistic particles travelling through the structure. Optimum pillar height and channel width have been determined. All required laser parameters and initial particle energy have been analytically estimated and a suitable laser as an energy source is proposed. Finally, the effect of fabrication error on the acceleration gradient is discussed.

Aim Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and potentially progresses to fatal thrombosis. The 4Ts scoring system has been reported as a clinical pretest for HIT. However, its usefulness in critically ill patients has not yet been thoroughly examined. Thus, we evaluated the clinical usefulness of the 4Ts score in the diagnosis of HIT in critically ill patients. Methods One hundred and four critically ill patients who were admitted to our intensive care unit and who underwent the antiplatelet factor 4/heparin complex antibodies (PF4/heparin Ab) test with suspected HIT were enrolled in the study. The primary endpoint variable was the 4Ts score. The secondary endpoint variables were laboratory data, length of stay, and mortality, compared between thePF4/heparin Ab positive and negative groups. Results There was no significant difference in the 4Ts scores between the PF4/heparin Ab positive and negative groups. The positive predictive value (HIT patients/4T high score patients) was 15.4% (2/13), the negative predictive value (non-HIT patients/4T low score patients) was 87.5% (42/48), and the false-negative rate for the 4Ts score (4T low score patients/HIT patients) was as high as 54.5% (6/11). The PF4/heparin Ab positive patients had longer stay in intensive care compared to the PF4/heparin Ab negative patients (P = 0.035). Conclusions The present study showed the discrepancy between the 4Ts score and PF4/heparin Ab. When HIT is suspected in critically ill patients, an immediate HIT antibody test and initiation of therapeutic management of HIT are required regardless of the 4Ts score.

Large arterial sheaths currently used for resuscitative endovascular balloon occlusion of the aorta (REBOA) may be associated with severe complications. Smaller diameter catheters compatible with 7Fr sheaths may improve the safety profile.A retrospective review of patients receiving REBOA through a 7Fr sheath for refractory traumatic hemorrhagic shock was performed from January 2014 to June 2015 at five tertiary-care hospitals in Japan. Demographics were collected including method of arterial access; outcomes included mortality and REBOA-related access complications.Thirty-three patients underwent REBOA at Zone 1 (level of the diaphragm). Most patients were male (70%), with a mean age (+SD) 50 ± 18 years, mean BMI 23 ± 4, and a median [IQR] ISS of 38 [34, 52]. Ninety-four percent of patients presented after sustaining injuries from blunt mechanisms. Twenty-four percent underwent CPR before arrival, and an additional 15% received CPR after admission. Percutaneous arterial access without ultrasound or fluoroscopy was achieved in all patients. Systolic blood pressure increased significantly following balloon occlusion (mean 62 ± 36 to 106 ± 40 mm Hg, p0.001). Median total duration of complete initial occlusion was 26 [range 10-35] minutes. Sixteen patients (49%) survived beyond 24 hours, and 14 patients (42%) survived beyond 30 days. Twenty-four-hour and 30-day survival were 48% and 42%, respectively. Of the patients surviving 24 hours (n = 16), median duration of sheath placement was 28 [range 18-45] hours with all removed using manual pressure to achieve hemostasis. Of 33 REBOAs, 20 were performed by Emergency Medicine practitioners, 10 by Emergency Medicine practitioners with endovascular training, and 3 by Interventional Radiologists. No complication related to sheath insertion or removal was identified during the follow-up period, including dissection, pseudoaneurysm, retroperitoneal hematoma, leg ischemia, or distal embolism.7Fr REBOA catheters can significantly elevate systolic blood pressure with no access-related complications. Our results suggest that a 7Fr introducer device for REBOA may be a safe and effective alternative to large-bore sheaths, and may remain in place during the post-procedure resuscitative phase without sequelae.Therapeutic/care management, level V.

Background Whether temporal differences alter the clinical outcomes of patients with out-of-hospital cardiac arrest (OHCA) remains inconclusive. Furthermore, the relationship between time of day and resuscitation efforts is unknown. Methods We studied adult OHCA patients in the Survey of Survivors after Out-of-Hospital Cardiac Arrest in the Kanto Region (SOS-KANTO) 2012 study from January 2012 to March 2013 in Japan. The primary variable was 1-month survival. The secondary outcome variables were prehospital and in-hospital resuscitation efforts by bystanders, emergency medical services personnel, and in-hospital healthcare providers. Daytime was defined as 0701 to 1500 h, evening was defined as 1501 to 2300 h, and night was defined as 2301 to 0700 h. Results During the study period, 13,780 patients were included in the analysis. The patients with night OHCA had significantly lower 1-month survival compared to the patients with daytime OHCA (night vs. daytime, adjusted odds ratio (OR) 1.66; 95 % confidence interval (CI), 1.34–2.07; P

胸腰椎圧迫骨折の臨床経過と予後予測について検討を行った．過去2年間で受傷早期に来院し入院治療を行った43例50椎体（男性15例，女性28例）を対象とした．3カ月以上の疼痛持続の有無とX線学的に椎体圧潰率，局所後弯を受傷時と最終観察時に計測し，受傷時MRI（T1強調像），年齢，性別，受傷時椎体圧潰率，受傷時後弯度，損傷部位，受傷機転との関連を検討した．疼痛持続，椎体圧潰進行はMRI像の後壁損傷と男性症例に関連を認めた．後弯進行はMRI像の後壁損傷に関連を認めた．胸腰椎移行部の損傷は有意に椎体圧潰が進行していた．

【はじめに】X線上軽傷と思われた骨盤骨折後に大量の出血を生じ動脈塞栓術を要した2例を経験したので報告する．【症例1】87歳，女性．しりもちをついて受傷．X線では左恥骨上枝の単独骨折だった．CTで骨盤腔内に大量の出血を生じていた．造影CTでactive bleedingの所見だったため血管造影を行い両側の閉鎖動脈を塞栓した．処置中にショック症状を呈し輸血を行った．TAE後状態は安定し53日間で退院した．【症例2】85才，男性．2mの高さより転落して受傷．X線では左坐骨の単独骨折だった．造影CTでactive bleedingがみられたため血管造影を行い閉鎖動脈を塞栓した．処置中に血圧が低下し輸血を行った．TAE後状態は安定し38日で退院した．【結語】X線上軽傷と思われる骨盤骨折でも重傷化する症例があることを念頭に置くべきである．

Atraumatic splenic rupture (ASR) is an uncommon pathologic condition in which bleeding from the spleen occurs for a variety of nontraumatic reasons. While the current trend in traumatic splenic rupture is nonoperative management including transcatheter arterial embolization, the current recommendation for the treatment of most patients with ASR is splenectomy. In this report, we describe two cases of ASR presenting with hemorrhagic shock and complicated by anticoagulation therapy. In patients with severe hemorrhagic shock and coagulopathy, a damage control strategy is recommended. Our successful treatment of these patients included a three-step strategy as a damage control: (i) rapid transient hemostasis by splenic artery occlusion using a microballoon catheter, (ii) damage control resuscitation and (iii) splenectomy as a definitive hemostatic treatment.

An automated mesh refinement technique for body-fitted multiblock structured grids used in computational fluid dynamics (CFD) simulation has been developed. The present technique reads a baseline mesh with tens of millions of cells generated by conventional software with a graphical user interface (GUI) and can refine up to tens of billions of grid points. Each grid block is refined based on the non-uniform rational B-spline (NURBS) volume; therefore, a body with curvature, such as airfoil, can be refined without reading geometrical data for the body. This tool is capable of retaining the initial grid spacing of the first cell at the boundary layer on the wall and that of the far-field boundary through the mesh refinement process. This tool was parallelized using message passing interface (MPI), and a mesh with 8.2 billion points was generated for an aeroacoustic computation from a baseline mesh with 30 million of points within 4 min using 288 cores of a PC cluster.

PurposeThe final decision for discharge from the intensive care unit (ICU) is uncertain because it is made according to various patient parameters; however, it should be made on an objective evaluation. Previous reports have been inconsistent and unreliable in predicting post-ICU mortality. To identify predictive factors associated with post-ICU mortality, we analyzed physiological and laboratory data at ICU discharge.MethodsPatients admitted to our ICU between September 2012 and August 2013 and staying for critical care>2 days were included. Sequential Organ Failure Assessment (SOFA) score; systemic inflammatory response syndrome score; white blood cell count; and serum C reactive protein, procalcitonin (PCT), interleukin-6 (IL-6), lactate, albumin, and hemoglobin levels were recorded. The primary end point was 90-day mortality after ICU discharge. Two hundred eighteen patients were enrolled (195 survivors, 23 non-survivors).ResultsNon-survivors presented a higher SOFA score and serum PCT, and IL-6 levels, as well as lower serum albumin and hemoglobin levels. Serum PCT, albumin, and SOFA score were associated with 90-day mortality in multiple logistic regression analysis. Hosmer-Lemeshow test showed chi-square value of 6.96, and P value of 0.54. The area under the curve (95% confidence interval) was 0.830 (0.771-0.890) for PCT, 0.688 (0.566-0.810) for albumin, 0.861 (0.796-0.927) for SOFA score, and increased to 0.913 (0.858-0.969) when these were combined. Serum PCT level at 0.57 ng/mL, serum albumin at 2.5 g/dL and SOFA score at 5.5 predict 90-day mortality, and high PCT, low albumin and high SOFA groups had significantly higher mortality. Serum PCT and SOFA score were significantly associated with survival days after ICU discharge in Cox regression analysis.ConclusionsSerum PCT level and SOFA score at ICU discharge predict post-ICU mortality and survival days after ICU discharge. The combination of these two and albumin level might enable accurate prediction.

Inhibition of the renal sodium glucose cotransporter (SGLT) increases urinary glucose excretion (UGE) and thus reduces blood glucose levels during hyperglycemia. To explore the potential of new antihyperglycemic agents, we synthesized and determined the human SGLT2 (hSGLT2) inhibitory potential of novel substituted 3-benzylindole-N-glucosides 6. Optimization of 6 resulted in the discovery of 3-(4-cyclopropylbenzyl)-4-fluoroindole-N-glucoside 6a-4 (TA-1887), a highly potent and selective hSGLT2 inhibitor, with pronounced antihyperglycemic effects in high-fat diet-fed KK (HF-KK) mice. Our results suggest the potential of indole-N-glucosides as novel antihyperglycemic agents through inhibition of renal SGLT2.

article i nfo Purpose: Interleukin 6 (IL-6) is a proinflammatory cytokine produced during infections. We hypothesized that IL-6 levels in the cerebrospinal fluid (CSF) would be elevated in bacterial meningitis and useful for diagnosing and predicting neurologic outcomes. Materials and methods: For the differentiation of bacterial meningitis, serum and CSF samples were obtained from patients with an altered level of consciousness. Patients were classified into 3 groups: bacterial meningitis, nonbacterial central nervous system disease, and other site sepsis. Results: Of the 70 patients included in this study, there were 13 in the bacterial meningitis group, 21 in the nonbacterial central nervous system disease group, and 36 in the other site sepsis group. The CSF IL-6 level was significantly higher in the bacterial meningitis group than in the other 2 groups (P b .0001). Of the 5 CSF parameters assessed, CSF IL-6 level exhibited the largest area under the receiver operating characteristic curve (0.962), with a cut-off value of 644 pg/mL (sensitivity, 92.3%; specificity, 89.5%). To examine a potential association between a high CSF level and neurologic outcome, CSF IL-6 levels were divided into 4 quartiles, and each level was compared with the frequency of a good neurologic outcome. The frequency of a good neurologic outcome was significantly lower in the highest CSF IL-6 quartile than in the other 3 quartiles (odds ratio, 0.18; 95% confidence interval, 0.05-0.69; P = .013). Conclusions: Measurement of the CSF IL-6 level is useful for diagnosing bacterial meningitis.

In order to estimate the health risk associated with a low dose radiation, the fundamental process of the radiation effects in a living cell must be understood. It is desired that an electron bunch or photon pulse precisely knock a cell nucleus and DNA. The required electron energy and electronic charge of the bunch are several tens keV to 1 MeV and 0.1 fC to 1 fC, respectively. The smaller beam size than micron is better for the precise observation. Since the laser-driven dielectric electron accelerator seems to suite for the compact micro-beam source, a phase-modulation-masked-type laser-driven dielectric accelerator was studied. Although the preliminary analysis made a conclusion that a grating period and an electron speed must satisfy the matching condition of LG/λ = v/c, a deformation of a wavefront in a pillar of the grating relaxed the matching condition and enabled the slow electron to be accelerated. The simulation results by using the free FDTD code, Meep, showed that the low energy electron of 20 keV felt the acceleration field strength of 20 MV/m and gradually felt higher field as the speed was increased. Finally the ultra relativistic electron felt the field strength of 600 MV/m. The Meep code also showed that a length of the accelerator to get energy of 1 MeV was 3.8 mm, the required laser power and energy were 11 GW and 350 mJ, respectively. Restrictions on the laser was eased by adopting sequential laser pulses. If the accelerator is illuminated by sequential N pulses, the pulse power, pulse width and the pulse energy are reduced to 1/N, 1/N and 1/N2, respectively. The required laser power per pulse is estimated to be 2.2 GW when ten pairs of sequential laser pulse is irradiated.

A collaborative randomized clinical trial on the intravesical administration of Adriamycin (ADM) with or without verapamil (VR), a calcium-channel blocker, as chemotherapy of superficial bladder cancer (Ta, T1) was carried out at two universities, Okayama and Kagoshima, and their affiliated hospitals. Arm A consisted of ADM given at 50 mg/50 ml saline, and arm B consisted of ADM given at 50 mg/40 ml saline plus five ampules (25 mg/10 ml saline) of injectable VR. The drugs were instilled into the bladder for 3 consecutive days, and three such courses were given with a 4-day interval between each course for a total of nine instillations. A total of 96 patients (48 in arm A and 48 in arm B) were entered into this study. The two treatment groups showed no significant difference in background factors. Of the 40 evaluated arm-A patients, 24 (60.0%) showed a response (CR + PR), whereas 19 (48.7%) of the 39 patients in arm B responded. The difference between these response rates was not statistically significant. As for adverse reactions to the intravesical chemotherapy, local inflammatory symptoms were observed in half of the patients, although no systemic reaction was observed. No significant difference was found between arm A and arm B, except for urinary turbidity. In conclusion, at the dose employed in the present clinical trial, there was no clear enhancement of the effect of ADM combined with VR in patients with superficial bladder cancer. Further clinical studies are required to determine the optimal doses of ADM and VR for their combination in intravesical chemotherapy.

The Japanese Urological Cancer Research Group for Adriamycin has conducted a series of clinical trials to investigate the efficacy and safety of prophylactic intravesical chemotherapy for superficial bladder cancer. In the third trial, reported herein, patients with recurrent bladder cancer or multiple primary cancer were selected and randomized to one of four groups using the envelope method after complete resection of the original tumors. Group A was given Adriamycin alone, group B received oral 5-fluorouracil (5-FU), group C was given Adriamycin and oral 5-FU, and group D served as the control group. Of the 544 patients registered, 331 were evaluable for the purpose of this study. The administration of 5-FU (group B) failed to prevent the recurrence of bladder tumors. Although group C (both Adriamycin and 5-FU) did not fare better than group A (Adriamycin only), Adriamycin was effective in preventing the recurrence of tumors, especially in high-risk patients with recurrent and multiple tumors. The risk of recurrence was reduced to 0.21 (95% confidence interval, 0.10–0.44) relative to the control group. There was no indication of a synergistic effect between 5-FU and Adriamycin. As side effects, cystitis syndrome was observed in 23%–30% of the patients in the Adriamycin groups and mild myelosuppression was observed in the 5-FU groups.

A multicenter cooperative study was conducted to evaluate the clinical efficacy and safety ofcis-diammine(glycolato)platinum (254-S), a second-generation anticancer platinum complex, in the treatment of genitourinary cancers. 254-S was given i. v. at 100 mg/m2 at 4-week intervals. As a result, 2 complete responses (CRs) and 8 partial responses (PRs) were obtained in 35 patients with transitional-cell carcinoma (TCC) of the urinary bladder or pyeloureter, 3 PRs were obtained in 16 subjects with prostatic cancer, and 6 CRs and 6 PRs were obtained in 15 patients with testicular cancer, generating objective response rates of 28.6% [95% confidence interval (CI), 14.6%–46.3%], 18.8% (95% CI, 4.0%–45.6%), and 80.0% (95% CI, 51.9%–95.7%), respectively. Bone marrow suppression was the dose-limiting toxicity, although it was reversible. Although no hydration was performed in approx. 40% of the patients, the incidence of nephrotoxic effects was low and most of those encountered were mild, the exception being one patient who showed severe renal insufficiency after the first treatment. Nausea and vomiting occurred in approx. 70% of the patients, but most gastrointestinal toxicities were controlled without antiemetic treatment. In addition, liver-function impairment was rarely observed. We conclude that 254-S is a promising cisplatin analogue for the treatment of genitourinary cancers and is worthy of further investigation in large-scale, randomized comparative studies with other platinum derivatives in both single-agent and combination regimens.

A randomized prospective study was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancers. Eligible patients were randomized into three groups: 1) adriamycin (ADM) group; intravesical instillation with 50 mg of ADM dissolved in 100 ml physiological saline, 2) mitomycin C (MMC) group; intravesical instillation with 30 mg of MMC dissolved in 100 ml of physiological saline, 3) control group; transurethral resection or transurethral coagulation only. The characteristic features of our protocol consisted of frequent (six times) instillations of the drugs within two weeks after transurethral resection, followed by instillations on two consecutive days at four-week intervals for two years. Furthermore, large quantities (100 ml) of instillation fluid containing relatively low concentrations of the drugs (500 micrograms/ml for ADM or 300 micrograms/ml for MMC) were employed. One hundred and forty-four patients have been submitted to the study; 110 patients were fully evaluable for recurrence and 34 patients were eliminated as non-evaluable patients. The cumulative five-year non-recurrence rates of the patients with multiple tumors were 32% in the MMC group, 25% in the ADM group and 7% in the control group. The cumulative non-recurrence rates of the ADM and MMC groups were significantly higher than that of the control group. It is considered that this instillation therapy with ADM and MMC is useful for preventing the recurrence of superficial bladder cancers.

Long-term results were analyzed in terms of tumor progression and survival in patients with superficial bladder cancer who were enrolled in the second intravesical chemoprophylactic study of the Japanese Urological Cancer Research Group for Adriamycin, which was started in July 1982. This study was a prospective, randomized, controlled trial conducted on primary tumors treated with a long-term instillation regimen that involved control versus intravesical instillations of Adriamycin or mitomycin C given once a week for the first 2 weeks, once every other week for 14 weeks, once a month for 8 months, and once every 3 months for 1 year, for a total of 21 instillations in 2 years. An analysis of the prophylactic effects of such treatment on bladder tumors after TUR has previously been performed, and the results have been published elsewhere. The present study represents a follow-up of the above trial. Of the 671 cases previously analyzed with regard to tumor prophylaxis, 158 cases (23.5%) were eligible to be followed for tumor progression and survival. A detailed comparison of the background factors between these 158 patients and the other 513 cases revealed no statistically significant difference. Thus, the 158 evaluable cases might reasonably be considered to represent all patients enrolled in the second study, and the results were thought to be reasonable enough to reflect the long-term efficacy of the long-term instillation regimen adopted in this study. The median follow-up for these 158 cases was 6.6 years. Tumor progression in terms of the disease stage and/or grade occurred in 43 of 127 patients who received prophylactic instillations and in 12 of 31 control cases. No significant difference in the incidence of tumor progression was found between the treatment and the control groups. In addition, no difference in survival was observed between the treatment group and the control group. Survival was also compared between patients who showed tumor progression and those who did not. All patients whose tumors did not progress survived, whereas the 7-year survival of those exhibiting tumor progression was less than 90%.