The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma.

BACKGROUND: The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. METHODS: This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. RESULTS: The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. CONCLUSIONS: Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. TRIAL REGISTRATION NUMBER: umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.

Delayed massive bleeding from minor splenic injury due to mechanical chest compression for cardiopulmonary resuscitation.

Background: Splenic injury due to chest compressions is a rare and fatal complication that occurs immediately after cardiopulmonary resuscitation. Case Presentation: Cardiopulmonary resuscitation was carried out using a mechanical chest compression device in a 74-year-old Japanese female patient who underwent cardiac arrest. Computed tomography postresuscitation revealed bilateral anterior rib fractures. Other traumatic findings were not observed. Coronary angiography revealed no new lesions; the cause of the arrest was hypokalemia. She received mechanical support with venoarterial extracorporeal membrane oxygenation and multiple antithrombotic agents. Her hemodynamic and coagulative condition became life-threatening on day 4; abdominal ultrasound revealed massive bloody ascites. Only a minor splenic laceration was observed intraoperatively, despite massive bleeding. Furthermore, her condition stabilized after splenectomy and blood transfusion. Venoarterial extracorporeal membrane oxygenation was discontinued on day 5. Conclusion: In patients with postcardiac arrest, delayed bleeding due to minor visceral injury should be considered, particularly for coagulation abnormalities.

Dosimetric Comparison of Helical Tomotherapy, Volumetric-Modulated Arc Therapy, and Intensity-Modulated Proton Therapy for Angiosarcoma of the Scalp.

OBJECTIVE: We compared radiotherapy plans among helical tomotherapy (HT), volumetric-modulated arc therapy (VMAT), and intensity-modulated proton therapy (IMPT) for angiosarcoma of the scalp (AS). METHODS: We conducted a planning study for 19 patients with AS. The clinical target volume (CTV) 1 and CTV2 were defined as the gross tumor volume with a specific margin and total scalp, respectively. For HT and VMAT, the planning target volume (PTV) 1 and PTV2 were defined as CTV1 and CTV2 with 0.5-cm margins, respectively. For IMPT, robust optimization was used instead of a CTV-PTV margin (i.e. CTV robust). The targets of the HT and VMAT plans were the PTV, whereas the IMPT plans targeted the CTV robust. In total, 70 Gy and 56 Gy were prescribed as the D95% (i.e. dose to 95% volume) of PTV1 (or CTV1 robust) and PTV2 (or CTV2 robust), respectively, using the simultaneous integrated boost (SIB) technique. Other constraint goals were also defined for the target and organs at risk (OAR). RESULTS: All dose constraint parameters for the target and OAR met the goals within the acceptable ranges for the 3 techniques. The coverage of the targets replaced by D95% and D98% were almost equivalent among the 3 techniques. The homogeneity index of PTV1 or CTV1 robust was equivalent among the 3 techniques, whereas that of PTV2 or CTV2 robust was significantly higher in the IMPT plans than in the other plans. IMPT reduced the Dmean of the brain and hippocampus by 49% to 95%, and the Dmax of the spinal cord, brainstem, and optic pathway by 70% to 92% compared with the other techniques. CONCLUSION: The 3 techniques with SIB methods provided sufficient coverage and satisfactory homogeneity for the targets, but IMPT achieved the best OAR sparing.

Prehospital lactate improves prediction of the need for immediate interventions for hemorrhage after trauma.

The blood lactate level is used to guide the management of trauma patients with circulatory disturbance. We hypothesized that blood lactate levels at the scene (Lac scene) could improve the prediction for immediate interventions for hemorrhage. We prospectively measured blood lactate levels and assessed retrospectively in 435 trauma patients both at the scene and on arrival at the emergency room (ER) of a level I trauma center. Primary outcome was immediate intervention for hemorrhage defined as surgical/radiological intervention and/or blood transfusion within 24 h. Physiological variables plus Lac scene significantly increased the predictive value for immediate intervention (area under the curve [AUC] 0.882, 95% confidence interval [CI] 0.839-0.925) compared to that using physiological variables only (AUC 0.837, 95% CI 0.787-0.887, P = 0.0073), replicated in the validation cohort (n = 85). There was no significant improvement in predicting value of physiological variables plus Lac scene for massive transfusion compared to physiological variables (AUC 0.903 vs 0.895, P = 0.32). The increased blood lactate level per minute from scene to ER was associated with increased probability for immediate intervention (P < 0.0001). Both adding Lac scene to physiological variables and the temporal elevation of blood lactate levels from scene to ER could improve the prediction of the immediate intervention.

Development of twist-correction system for radiotherapy of head and neck cancer patients.

To propose a concept for correcting the twist between the head and neck and the body frequently occurring in radiotherapy patients and to develop a prototype device for achieving this. Furthermore, the operational accuracy of this device under no load was evaluated. We devised a concept for correcting the twist of patients by adjustment of the three rotation (pitch, roll, and yaw) angles in two independent plates connected by a joint (fulcrum). The two plates (head and neck plate and body plate) rotate around the fulcrum by adjusting screws under each of them. A prototype device was created to materialize this concept. First, after all adjusting screws were set to the zero position, the rotation angle of each plate was measured by a digital goniometer. Repeatability was evaluated by performing 20 repeated measurements. Next, to confirm the rotational accuracy of each plate of the prototype device, the calculated rotation angles for 20 combinations of patterns of traveled distances of the adjusting screws were compared with those measured by the digital goniometer and cone-beam computed tomography (CT). The repeatability (standard deviation: SD) of the pitch, roll, and yaw angles of the head and neck plate was 0.04°, 0.05°, and 0.03°, and the repeatability (SD) of the body plate was 0.05°, 0.04°, and 0.04°, respectively. The mean differences ± SD between the calculated and measured pitch, roll, and yaw angles for the head and neck plate with the digital goniometer were 0.00 ± 0.06°, -0.01 ± 0.06°, and -0.04 ± 0.04°, respectively. The differences for the body plate were -0.03 ± 0.04°, 0.03 ± 0.05°, and 0.02 ± 0.05°, respectively. Results of the cone-beam CT were similar to those of the digital goniometer. The prototype device exhibited good performance regarding the rotational accuracy and repeatability under no load. The clinical implementation of this concept is expected to reduce the residual error of the patient position due to the twist.

Geometric discrepancy of image-guided radiation therapy in patients with prostate cancer without implanted fiducial markers using a commercial pseudo-CT generation method.

MR-only simulations provide pseudo-CT images which are segmented into 5 kinds of tissues from DIXON-based images. However, it is difficult to register pseudo-CT images to cone-beam CT (CBCT) images collected for image-guided radiation therapy (IGRT), because of the lack of contrasts among tissues. We validated gaps of IGRT between pseudo-CT or planning CT and CBCT for patients without implanted markers. We also propose calcification-assisted registration for MR-only simulation. We conducted retrospective analyses to verify the registration accuracy in 15 patients who underwent volumetric modulated arc therapy (VMAT) for prostate cancer. They underwent planning CT and pseudo-CT. Pseudo-CT images after deformable image registration (DIR) to planning CT images were rendered automatic pelvic bone matching to CBCT images. Patient positions on the pseudo-CT images after DIR were shifted on the basis of tissues around the prostate. We compared registration gaps between the images of planning CT and pseudo-CT with DIR, assuming that the tissue-based matching between the planning CT and CBCT was the gold standard. To the pseudo-CT images with DIR, calcifications detected on planning CT were added. We validated IGRT accuracy for a calcification-assisted registration. The absolute registration errors of the pseudo-CT, in comparison with the planning CT, were 0.34 ± 0.50 (lateral), 1.3 ± 1.3 (longitudinal), and 1.1 ± 1.0 mm (vertical). The absolute registration errors of the pseudo-CT with calcification contouring, in comparison with the planning CT, were 0.41 ± 1.0 (lateral), 0.87 ± 0.92 (longitudinal), and 0.74 ± 0.64 mm (vertical). Reduced absolute registration errors were observed in the proposed approach in the longitudinal (P < 0.01) and vertical (P < 0.01) dimensions when using calcification-assisted registration. The tissue-based registration using the MR-only simulation was not sufficient for use in patients with prostate cancer without implanted markers. The calcification-assisted registration might help to improve IGRT accuracy using MRI alone.

Multi-institutional comparison of secondary check of treatment planning using computer-based independent dose calculation for non-C-arm linear accelerators.

PURPOSE: This report covers the first multi-institutional study of independent monitor unit (MU)/dose calculation verification for the CyberKnife, Vero4DRT, and TomoTherapy radiotherapy delivery systems. METHODS: A total of 973 clinical treatment plans were collected from 12 institutions. Commercial software employing the Clarkson algorithm was used for verification after a measurement validation study, and the doses from the treatment planning systems (TPSs) and verification programs were compared on the basis of the mean value ±â€¯two standard deviations. The impact of heterogeneous conditions was assessed in two types of sites: non-lung and lung. RESULTS: The dose difference for all locations was 0.5 ±â€¯7.2%. There was a statistically significant difference (P < 0.01) in dose difference between non-lung (-0.3 ±â€¯4.4%) and lung sites (3.5 ±â€¯6.7%). Inter-institutional comparisons showed that various systematic differences were associated with the proportion of different treatment sites and heterogeneity correction. CONCLUSIONS: This multi-institutional comparison should help to determine the departmental action levels for CyberKnife, Vero4DRT, and TomoTherapy, as patient populations and treatment sites may vary between the modalities. An action level of ±5% could be considered for intensity-modulated radiation therapy (IMRT), non-IMRT, and volumetric modulated arc radiotherapy using these modalities in homogenous and heterogeneous conditions with a large treatment field applied to a large region of homogeneous media. There were larger systematic differences in heterogeneous conditions with a small treatment field because of differences in heterogeneity correction with the different dose calculation algorithms of the primary TPS and verification program.

Interfacility variation in treatment planning parameters in tomotherapy: field width, pitch, and modulation factor.

Several studies have reported changes in dose distribution and delivery time based on the value of specific planning parameters [field width (FW), pitch, and modulation factor (MF)] in tomotherapy. However, the variation in the parameters between different facilities is unknown. The purpose of this study was to determine standard values of the above parameters for cases of head and neck cancer (HNC) and prostate cancer (PC) in Japan. In this survey, a web-based questionnaire was sent to 48 facilities performing radiation therapy with tomotherapy in March 2016. The deadline for data submission was April 2016. In the questionnaire, the values of the planning parameters usually used were requested and 23 responses were received, representing a response rate of 48% (23/48). The FW selected was 2.5 cm in most facilities, and facilities with a tomoEDGE license used dynamic FW rather than fixed FW. Facilities changed the pitch based on FW, dose per fraction, or target offset more frequently in HNC than in PC. In contrast, >50% of the facilities used the magic number proposed by Kissick et al. Median preset MFs (range, min to max) in HNC and PC were 2.4 (1.8-2.8) and 2.0 (1.8-3.0), respectively, and MF values showed large variations between the facilities. Our results are likely to be useful to several facilities designing treatment plans in tomotherapy.

Development of a novel information and communication technology system to compensate for a sudden shortage of emergency department physicians.

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 < 0.0001). On the whole, the probability of multiple casualties increased more than 2 times after system introduction 6.2% vs. 13.6%, P < 0.0001). DISCUSSION: After introducing the system, probability of multiple casualties increased. Thus the system may contribute to improvement in the ability to respond to sudden excessive patient needs in multiple causalities. CONCLUSIONS: A novel system using ICT successfully secured immediate responses from needed physicians outside the hospital without increasing user workload, and increased the ability to respond to excessive patient needs. The system appears to be able to compensate for a shortage of physician in the ED due to excessive patient transfers, particularly during off-hours.

Case Report: Urgent endovascular treatment of subclavian artery injury after blunt trauma.

Subclavian arterial injury is rare and potentially life-threatening, particularly when it leads to arterial occlusion, causing limb ischemia, retrograde thromboembolization and cerebral infarction within hours after injury. Here we report a blunt trauma case with subclavian arterial injury, upper extremity ischemia, and the need for urgent treatment to salvage the limb and prevent cerebral infarction. A 41-year-old man had a left, open, mid-shaft clavicle fracture and left subclavian artery injury accompanied by a weak pulse in the left radial artery, decreased blood pressure of the left arm compared to the right, and left hand numbness. Urgent debridement and irrigation of the open clavicle fracture was followed by angiography for the subclavian artery injury. The left distal subclavian artery had a segmental dissection with a thrombus. Urgent endovascular treatment using a self-expanding nitinol stent successfully restored the blood flow and blood pressure to the left upper extremity. Endovascular treatment is a viable option for cases of subclavian artery injury where there is a risk of extremity ischemia and cerebral infarction.

Prediction of back-scatter radiations to a beam monitor chamber of medical linear accelerators by use of the digitized target-current-pulse analysis method.

In small-field irradiation, the back-scattered radiation (BSR) affects the counts measured with a beam monitor chamber (BMC). In general, the effect of the BSR depends on the opened-jaw size. The effect is significantly large in small-field irradiation. Our purpose in this study was to predict the effect of BSR on LINAC output accurately with an improved target-current-pulse (TCP) technique. The pulse signals were measured with a system consisting of a personal computer and a digitizer. The pulse signals were analyzed with in-house software. The measured parameters were the number of pulses, the change in the waveform and the integrated signal values of the TCPs. The TCPs were measured for various field sizes with four linear accelerators. For comparison, Yu's method in which a universal counter was used was re-examined. The results showed that the variance of the measurements by the new method was reduced to approximately 1/10 of the variance by the previous method. There was no significant variation in the number of pulses due to a change in the field size in the Varian Clinac series. However, a change in the integrated signal value was observed. This tendency was different from the result of other investigations in the past. Our prediction method is able to define the cutoff voltage for the TCP acquired by digitizer. This functionality provides the capability of clearly classifying TCPs into signals and noise. In conclusion, our TCP analysis method can predict the effect of BSR on the BMC even for small-field irradiations.

[Analysis of radioactivation induced by high-energy X-rays in medical linear accelerators -estimation of short-lived radioactivated nuclides-].

In medical linear accelerators, radioactivation is induced on the target and neighborhood parts by photoneutrons accompanying a photo-nuclear reaction and leading to higher acceleration energy. We measured the residual radiation from the radioactivated materials according to the time, and tried to identify radioactivated nuclides and their relative quantities by means of measurement results. It was presumed that the main source of residual radiations was the Target, Flattening filter and Primary collimator in the linac head. Among those materials (copper, tungsten), we calculated decrement curves of residual radiations from radioactivated nuclides generated with photo-nuclear reaction or thermal neutron capture reaction by various ratios, and we investigated the ratio that best fit the measured data. Consequently, it was presumed that (66)Cu generated with thermal neutron capture reaction contributed the most to residual radiation, followed by (62)Cu generated with photo-nuclear reaction contributed. It is important to understand various characteristics of these nuclides and to undertake management of the device.

[Analysis of photonuclear activation effect of high-energy medical linear accelerators--measurement of spatial dose distribution and temporal decay curve, and assessment of personnel dosimetry].

The characteristics of activation after high-energy X-rays have been generated by medical linear accelerators were measured using an ionization chamber. Radiation doses increased with rising X-ray energy, based on 10 MV, 15 MV, and 18 MVX-ray measurements. When the total irradiation dose was changed, radiation dose increased with total irradiation dose. When the collimator opened, the radiation dose at a position 15 cm from the isocenter reached about the maximum, which was 2.2 times the dose at the isocenter. The radiation dose became about 0.3 times its level at a position 40 cm from the isocenter, in the outer irradiation field. The dose distribution in the treatment room became almost the same dose extending from the isocenter to 200 cm. Radiation dose decreased gradually while moving away from the target on the treatment beam axis. But it increased again as it approached the floor face. The occupational exposure dose, which was presumed from measurements of the radiation dose 50 cm from the isocenter, was about 0.9 mSv during a year, assuming 600 MU for 1 person, 8 people a day, and 245 days a year. Radiation dose changed with X-ray energy in the machine used, and it was a geometrical constituent in the treatment room. It is important to understand the characteristics of radiation generated by medical linear accelerators.

Influence of contrast materials on dose calculation in radiotherapy planning using computed tomography for tumors at various anatomical regions: a prospective study.

Influences of iodinated contrast media on dose calculation were studied in 26 patients. Mean increases in monitor units by contrast media administration were less than 1% and considered negligible in planning of whole-brain, whole-neck, mediastinal, and whole-pelvic irradiation. However, mean increases over 2% were seen in planning of upper-abdominal radiotherapy.