Usefulness of Self-Selected Scenarios for Simple Triage and Rapid Treatment Method Using Virtual Reality.

BACKGROUND: Repeated triage training is necessary to maintain and improve the accuracy of simple triage and rapid treatment (START), a popular triage method. Virtual reality (VR) may be more effective than conventional training methods. This study aimed to verify the educational usefulness of START using VR originally developed for students. METHODS: A VR was initially developed with a function that allowed students to select the triage procedure and its evaluation. Triage was performed using a simple modified START method, and eight scenarios were developed. The participants included 70 paramedic students classified into VR and live lecture groups. They took a 20-question written test that evaluated their academic ability before the course. After the course, a practical test and a 20-question written test were conducted. The total score of the practical test was 43 points. Triage procedure (1 point), observation and evaluation (1-5 points), and triage categories (1 point) were evaluated in this test. RESULTS: The VR and live lecture groups consisted of 33 and 29 participants, respectively. No significant differences were observed pre- and post-test. In the practical test, the median (interquartile range) score was 29 (26-32) and 25 (23-29) for the VR and live lecture groups, respectively, with the VR group scoring significantly higher (P=0.03). CONCLUSION: Our results confirmed the educational usefulness of selective VR for active learning of START. Therefore, VR combined with live lectures and simulations would be an optimal educational technique.

A Study on Points of Respiratory Assist Devices Using in Pre-Hospital Care Respiratory Assist Devices in Pre-Hospital Care.

BACKGROUND: In Japan, increasing the number of ambulance requests, the case with the use of respiratory assistance devices in prehospital care by paramedics is also increasing1. When patient experiences respiratory failure, the first responders frequently select a respiratory assist device (RAD) such as Bag Valve Mask (BVM), Jackson Rees (JR), or BVM with Gas Supply Valve® (BVM+GSV). This is based on both evaluation and experience as there is no study indicating which RAD is the best choice at the pre-hospital emergency site. This study clarified the precautions when using BVM, JR, and BVM+GSV in pre-hospital emergency medical care with healthy volunteers. METHODS: Twenty healthy adults were fitted with a RAD while breathing spontaneously, and changes in vital signs and ETCO2 were observed. RESULTS: The level of ETCO2 became elevated after each RAD was attached. The value was significantly higher in the JR group than in the others. CONCLUSIONS: The study showed that even in the presence of spontaneous breathing, ETCO2 increased markedly with the application of respiratory assist devices that are used in pre-hospital care for conditions such as hypoxemia and ventilatory disturbance. The increase in ETCO2 was particularly significant in the JR group, suggesting the need for caution when selecting JRs for pre-hospital care. As the number of subjects was only 20 for each RAD, studies with a larger sample size are needed.

Accuracy of breathing and radial pulse assessment by non-medical persons: an observational cross-sectional study.

Early recognition of cardiopulmonary arrest (CPA) expedites emergency calls and resuscitation and improves the survival rate of unresponsive individuals. However, the accuracy of breathing and radial artery pulse assessment by non-medical persons is poorly understood. The aim of this study was to determine the accuracy of breathing assessment and radial pulse palpation among 450 non-medical personnel using a high-fidelity simulator. We examined the accuracy of 10 second's assessment for breathing and radial pulse using a high-fidelity mannequin simulator, included 496 non-medical participants (school teachers) between 2016-2018. For a primary results, the sensitivity for the detection of the presence of the breathing and radial pulse was 96.2% (97.5% for sensitivity and 92.0% for specificity) and 91.7% (99.1% for sensitivity and 56.8% for specificity), respectively. Futher, breathing rate and radial pulse rate were strongly correlated with the assessments, with Spearman's correlation coefficients of 0.813 (P < 0.001) and 0.719 (P < 0.001), respectively. In contrast, radial pulse strength was weakly correlated with the assessment (coefficient of 0.288, P < 0.001). Our results suggested that non-medical persons would show high accuracy in detecting and measuring respiration and radial pulse, although they did not accurately determine radial pulse strength for the early recognition of CPA.

Evaluation of outcomes after EMS-witnessed traumatic out-of-hospital cardiac arrest caused by traffic collisions.

AIM: The survival rate of patients with traumatic cardiac arrest is 3% or lower. Cardiac arrest witnessed by emergency medical services (EMS) accounts for approximately 16% of prehospital traumatic cardiac arrests, but the prognosis is unknown. We aimed to compare the 1-month survival rate of cardiac arrest witnessed by EMS with that of cardiac arrest witnessed by bystanders and unwitnessed cardiac arrest in traffic trauma victims; further, the time from injury to cardiac arrest was assessed. METHODS: This analysis used the Utstein Registry in Japan and included data of 3883 patients with traumatic cardiac arrest caused by traffic collisions registered between 2014 and 2019 in Japan. RESULTS: The 1-month survival rate was 10.9% in the EMS-witnessed cardiac arrest group; this was significantly higher than that in the bystander-witnessed (7.2%) and unwitnessed (5.6%) cardiac arrest groups (P < 0.01). The median time from injury to cardiac arrest was 18 min (25% quartile: 12, 75% quartile: 26). CONCLUSION: The 1-month survival rate was significantly higher in the EMS-witnessed cardiac arrest group than in the bystander-witnessed and unwitnessed cardiac arrest groups. It is important to prevent progression to cardiac arrest in trauma patients with intact respiratory function and pulse rate at the time of contact with EMS. A system for early recognition of severe trauma is needed, and a doctor's car or helicopter can be requested as needed. We believe that early recognition and prompt intervention will improve the prognosis of prehospital traumatic cardiac arrest.

Wearing a face mask during controlled-intensity exercise is not a risk factor for exertional heatstroke: A pilot study.

AIM: This study aimed to measure the influence of wearing face masks on individuals' physical status in a hot and humid environment. METHODS: Each participant experienced different physical situations: (i) not wearing a mask (control), (ii) wearing a surgical mask, (iii) wearing a sport mask. An ingestible capsule thermometer was used to measure internal core body temperature during different exercises (standing, walking, and running, each for 20 min) in an artificial weather room with the internal wet-bulb globe temperature set at 28°C. The change in the participants' physical status and urinary liver fatty acid-binding protein (L-FABP) were measured. RESULTS: Six healthy male volunteers were enrolled in the study. In each participant, significant changes were observed in the heart rate and internal core temperatures after increased exercise intensity; however, no significant differences were observed between these parameters and urinary L-FABP among the three intervention groups. CONCLUSION: Mask wearing is not a risk factor for heatstroke during increased exercise intensity.

Cancer detection by ubiquitin carboxyl-terminal esterase L1 methylation in pancreatobiliary fluids.

AIM: To evaluate the utility of measuring epigenetic alterations in pancreatic and biliary fluids in determining molecular markers for pancreatobiliary cancers. METHODS: DNA was extracted from undiluted pancreatic and biliary fluids. As a surrogate for a genome-wide hypomethylation assay, levels of long interspersed nuclear element-1 (LINE-1) methylation were analyzed using bisulfite pyrosequencing. CpG island hypermethylation of 10 tumor-associated genes, aryl-hydrocarbon receptor repressor, adenomatous polyposis coli, calcium channel, voltage dependent, T type α1G subunit, insulin-like growth factor 2, O-6-methyl-guanine-DNA methyltransferase, neurogenin 1, CDKN2A, runt-related transcription factor 3 (RUNX3), secreted frizzled-related protein 1, and ubiquitin carboxyl-terminal esterase L1 (UCHL1), was analyzed using MethyLight. To examine the role of CpG methylation and histone deacetylation in the silencing of UCHL1, human gallbladder carcinoma cell lines and pancreatic carcinoma cell lines were treated with 2 or 5 µmol/L 5-AZA-dC for 72 h or 100 nmol/L Trichostatin A for 24 h. After the treatment, UCHL1 expression was analyzed by real-time reverse transcription-polymerase chain reaction. RESULTS: Pancreatobiliary cancers exhibited significantly lower LINE-1 methylation levels in pancreatic and biliary fluids than did noncancerous pancreatobiliary disease (58.7% ± 4.3% vs 61.7% ± 2.2%, P = 0.027; 53.8% ± 6.6% vs 57.5% ± 1.7%, P = 0.007); however, LINE-1 hypomethylation was more evident in pancreatic cancer tissues than in pancreatic fluids (45.4% ± 5.5% vs 58.7% ± 4.3%, P < 0.001). CpG island hypermethylation of tumor-associated genes was detected at various frequencies, but it was not correlated with LINE-1 hypomethylation. Hypermethylation of the UCHL1 gene was cancer-specific and most frequently detected in pancreatic (67%) or biliary (70%) fluids from patients with pancreatobiliary cancer. As a single marker, hypermethylation of the UCHL1 gene in pancreatic and biliary fluids was most useful for the detection of pancreatic and pancreatobiliary cancers, respectively (100% specificity). Hypermethylation of the UCHL1 and RUNX3 genes in pancreatic and biliary fluids was the most useful combined marker for pancreatic (87% sensitivity and 100% specificity) and pancreatobiliary (97% sensitivity and 100% specificity) cancers. Treatment with a demethylating agent, 5-AZA-2'-deoxycytidine, restored UCHL1 expression in pancreatobiliary cancer cell lines. CONCLUSION: Our results suggest that hypermethylation of UCHL1 and RUNX3 in pancreatobiliary fluid might be useful for the diagnosis of pancreatobiliary cancers.

Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer.

AIM: To investigate human epidermal growth factor receptor 2 (HER2)-phosphatidylinositol 3-kinase (PI3K)-v-Akt murine thymoma viral oncogene homolog signaling pathway. METHODS: We analyzed 231 formalin-fixed, paraffin-embedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment. The patients' age, sex, tumor location, depth of invasion, pathological type, lymph node metastasis, and pathological stage were determined by a review of the medical records. Expression of HER2 was analyzed by immunohistochemistry (IHC) using the HercepTest(TM) kit. Standard criteria for HER2 positivity (0, 1+, 2+, and 3+) were used. Tumors that scored 3+ were considered HER2-positive. Expression of phospho Akt (pAkt) was also analyzed by IHC. Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more. PI3K, catalytic, alpha polypeptide (PIK3CA) mutations in exons 1, 9 and 20 were analyzed by pyrosequencing. Epstein-Barr virus (EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA (EBER) with an EBER-RNA probe. Microsatellite instability (MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26. RESULTS: HER2 expression levels of 0, 1+, 2+ and 3+ were found in 167 (72%), 32 (14%), 12 (5%) and 20 (8.7%) samples, respectively. HER2 overexpression (IHC 3+) significantly correlated with intestinal histological type (15/20 vs 98 /205, P = 0.05). PIK3CA mutations were present in 20 cases (8.7%) and significantly correlated with MSI (10/20 vs 9/211, P < 0.01). The mutation frequency was high (21%) in T4 cancers and very low (6%) in T2 cancers. Mutations in exons 1, 9 and 20 were detected in 5 (2%), 9 (4%) and 7 (3%) cases, respectively. Two new types of PIK3CA mutation, R88Q and R108H, were found in exon1. All PIK3CA mutations were heterozygous missense single-base substitutions, the most common being H1047R (6/20, 30%) in exon20. Eighteen cancers (8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type (13/18 vs 93/198, P = 0.04). There were 7 cases of lymphoepithelioma-like carcinomas (LELC) and 6 of those cases were EBV-positive (percent/EBV: 6/18, 33%; percent/all LELC: 6/7, 86%). pAkt expression was positive in 119 (53%) cases but showed no correlation with clinicopathological characteristics. pAkt expression was significantly correlated with HER2 overexpression (16/20 vs 103/211, P < 0.01) but not with PIK3CA mutations (12/20 vs 107/211, P = 0.37) or EBV infection (8/18 vs 103/211, P = 0.69). The frequency of pAkt expression was higher in cancers with exon20 mutations (100%) than in those with exon1 (40%) or exon9 (56%) mutations. One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection. However, no cases showed both PIK3CA mutations and HER2 overexpression. One EBV-positive cancer with PIK3CA mutation (H1047R) was MSI-positive. Three of these 4 cases were positive for pAkt expression. In survival analysis, pAkt expression significantly correlated with a poor prognosis (hazard ratio 1.75; 95%CI: 1.12-2.80, P = 0.02). CONCLUSION: HER2 expression, PIK3CA mutations and EBV infection in gastric cancer were characterized. pAkt expression significantly correlates with HER2 expression and with a poor prognosis.

Co-expression of laminin ß3 and γ2 chains and epigenetic inactivation of laminin α3 chain in gastric cancer.

Laminin-332 (LM-332, formerly termed laminin-5) is a heterotrimeric glycoprotein that regulates cell adhesion and migration. Molecular alterations of LM-332 are involved in cancer progression. The aim of this study was to clarify alterations of LM-332 in gastric carcinoma. The expression of LM-332 subunits in 10 gastric carcinoma cell lines was investigated by RT-PCR, Western blotting, and immuno-cytochemical/immunofluorescent analyses. The promoter methylation status of LM-332-encoding genes (LAMA3, LAMB3 and LAMC2) was analyzed by methylation-specific PCR (MSP). The relationship between cell migration and LM-332 expression was assessed by the scratch assay. The expression of LM-332 was analyzed immunohistochemically in 90 gastric cancer tissues. Co-expression of laminin ß3 and γ2 chains was often observed in gastric carcinoma cell lines at mRNA and protein levels. In contrast, there was no expression of laminin α3 at either the mRNA or protein levels. Extra-cellular secretion of laminin ß3 and γ2 chains was found in 2 of the 10 cell lines. The LAMA3 gene was transcriptionally silenced by methylation of the promoter CpG islands in all of the cell lines, while the LAMB3 and LAMC2 genes were silenced in several cell lines. Treatment with a demethylating agent, 5-aza-2'-deoxycytidine (5-aza-dC), restored expression of the LM-332-encoding genes. Methylation frequency of LAMA3 was higher than those of the LAMB2 and LAMC2 genes in gastric cancer tissues. Migration distances were significantly correlated with cytoplasmic laminin γ2 chain expression. Immunohistochemistry showed frequent co-expression of laminin ß3 and γ2 chains in gastric carcinoma cells, which was significantly correlated with depth of invasion and advanced tumor stage. The results suggest that the laminin ß3 and γ2 chains accumulate intracellularly and play a role in gastric cancer progression, while epigenetic silencing of the laminin α3 chain may lead to inability to synthesize the basement membrane and may affect cancer cell invasion. Cancer cell motility appears to be associated with the cyto-plasmic laminin γ2 chain in vitro.

Epigenetic inactivation of calcium-sensing receptor in colorectal carcinogenesis.

Ca2+ is a chemopreventive agent for colon cancer. Ion transport systems are often altered in human cancer. The aim of this study was to clarify the alterations of calcium-sensing receptor (CASR), a member of the G protein-coupled receptor family, in colorectal carcinogenesis. We analyzed the expression of CASR in colorectal cancer cell lines and in cancer and adenoma tissues by RT-PCR and immunostaining. In addition, we analyzed methylation of the CASR promoter by using bisulfite sequence analysis and methylation-specific PCR. CASR mRNA and protein expression was significantly downregulated in most of the cancer cell lines. CpG islands were densely methylated in cancer cell lines with reduced CASR mRNA expression. Treatment with a demethylating agent, 5-aza-2'-deoxycytidine, and/or a histone deacetylase inhibitor, trichostatin A, restored CASR expression in the cancer cell lines. Disruption of CASR expression in CASR-unmethylated HCT-8 cells blocked the enhancing effect of Ca2+ on the cytotoxic response to 5-fluorouracil. CASR expression was observed in normal colonic epithelial cells and was retained in most adenoma tissues. CASR mRNA and protein expression was significantly downregulated in cancer tissues. There was an inverse relationship between CASR expression and degree of differentiation. Immunohistochemical CASR staining was reduced more predominantly in less-differentiated cancer tissues and/or in cancer cells at the invasive front, where nuclear/cytoplasmic ß-catenin was often localized. CASR methylation was detected in 69% of colorectal cancer tissues and 90% of lymph node metastatic tissues and was significantly correlated with reduced CASR expression. CASR methylation was also detected in 32% of advanced adenoma tissues but was detected in only 9% of adenoma tissues and was not detected in hyperplastic polyp tissues. CASR methylation seems to occur at an early stage and progress in colorectal carcinogenesis. The results suggest that epigenetic inactivation of CASR has an important role in colorectal carcinogenesis.

Absolute quantitation of myocardial blood flow with (201)Tl and dynamic SPECT in canine: optimisation and validation of kinetic modelling.

PURPOSE: 201Tl has been extensively used for myocardial perfusion and viability assessment. Unlike 99mTc-labelled agents, such as 99mTc-sestamibi and 99mTc-tetrofosmine, the regional concentration of 201Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of 201Tl using dynamic SPECT. METHODS: Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of 201Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K(1)) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments. RESULTS: Regional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBF(SPECT)) correlated well with the MBF values obtained by the radio-labelled microspheres (MBF(MS)) (MBF(SPECT) = -0.067 + 1.042 x MBF(MS), p < 0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression. CONCLUSION: Absolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using 201Tl and dynamic SPECT.

Quantitative mapping of basal and vasareactive cerebral blood flow using split-dose 123I-iodoamphetamine and single photon emission computed tomography.

A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (y(ml/100 g/min)=1.07x(ml/100 g/min)-1.14, r=0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest-rest study was 1.5+/-5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease.

[Estimation and optimization of the use of standard arterial input function for split-dose administration of N-isopropyl-p[123I]iodoamphetamine].

UNLABELLED: Use of a standard arterial input function and calibrating it by a single blood sample or a continuous arterial blood sample has been researched for a repeat CBF assessment with split-dose administration of N-isopropyl-p[123I]iodoamphetamine (IMP). METHODS: The study population consisted of 5 normal volunteers and 5 patients with cerebrovascular disease. IMP was injected twice (111 MBq/2 ml each) into the anti-cubital vein at a constant infusion speed for 1 min. The arterial input function was monitored during the study including a continuous measurement of radioactivity concentration of both the whole-blood and the octanol-soluble component (Real-Input Function, RIF). Standard input function was determined, and was calibrated either by a single blood sample or a continuous blood sample to estimate the Estimated-Input Function (EIF). Area-Under-the Curve (AUC) was then compared between RIF and EIF. RESULTS: In case EIF was estimated with a single blood sample, the minimum error of estimated AUC was obtained when calibrated at 7 minutes after either the 1st or 2nd injections. Deviation of AUC for [0, 30] was +/- 6.6%, and +/- 5.0%, respectively. If calibrated with a continuous blood sample, the minimum error of AUC with the continuous blood sampling period of 10 min for [0, 30] and [30, 60] was +/- 5.3% and +/- 4.0%, respectively. CONCLUSIONS: AUC of EIF with either a single or continuous blood sampling appeared to have reasonably small errors, suggesting the validity of the use of standardized input function in the split-dose IMP SPECT.