Identification of Ppy-lineage cells as a novel origin of pancreatic ductal adenocarcinoma.

The Ppy gene encodes pancreatic polypeptide (PP) secreted by PP- or γ-cells, which are a subtype of endocrine cells localised mainly in the islet periphery. For a detailed characterisation of PP cells, we aimed to establish PP cell lines. To this end, we generated a mouse model harbouring the SV40 large T antigen (TAg) in the Rosa26 locus, which is expressed upon Ppy-promoter-mediated Cre-loxP recombination. Whereas Insulin1-CreERT-mediated TAg expression in beta cells resulted in insulinoma, surprisingly, Ppy-Cre-mediated TAg expression resulted in the malignant transformation of Ppy-lineage cells. These mice showed distorted islet structural integrity at 5 days of age compared with normal islets. CK19+ duct-like lesions contiguous with the islets were observed at 2 weeks of age, and mice developed aggressive pancreatic ductal adenocarcinoma (PDAC) at 4 weeks of age, suggesting that PDAC can originate from the islet/endocrine pancreas. This was unexpected as PDAC is believed to originate from the exocrine pancreas. RNA-sequencing analysis of Ppy-lineage islet cells from 7-day-old TAg+ mice showed a downregulation and an upregulation of endocrine and exocrine genes, respectively, in addition to the upregulation of genes and pathways associated with PDAC. These results suggest that the expression of an oncogene in Ppy-lineage cells induces a switch from endocrine cell fate to PDAC. Our findings demonstrate that Ppy-lineage cells may be an origin of PDAC and may provide novel insights into the pathogenesis of pancreatic cancer, as well as possible therapeutic strategies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Association between lung contusion volume and acute changes in fibrinogen levels: A single-center observational study.

Aim: Organ tissue damage, including the lungs, may lead to acute coagulopathy. This study aimed to evaluate the association between lung contusion volume and serum fibrinogen level during the acute phase of trauma. Methods: We conducted an observational study using electronic medical records at a tertiary-care center between January 2015 and December 2018. We included patients with lung contusions on hospital arrival. We used three-dimensional computed tomography to calculate lung contusion volumes. The primary outcome was the lowest fibrinogen level measured within 24 h of hospital arrival. We evaluated the association between lung contusion volume and outcome with multivariable linear regression analysis. Also, we calculated the sensitivity and specificity of lung contusion volume in patients with a serum fibrinogen level of ≤150 mg/dL. Results: We identified 124 eligible patients. Their median age was 43.5 years, and 101 were male (81.5%). The median lung contusion volume was 10.9%. The median lowest fibrinogen level within 24 h from arrival was 188.0 mg/dL. After adjustment, lung contusion volume had a statistically significant association with the lowest fibrinogen level within 24 h from arrival (coefficient -1.6, 95% confidence interval -3.16 to -0.07). When a lung contusion volume of 20% was used as the cutoff, the sensitivity and specificity to identify fibrinogen depletion were 0.27 and 0.95, respectively. Conclusion: Lung contusion volume was associated with the lowest fibrinogen level measured within 24 h from hospital arrival. Measuring lung contusion volume may help to identify patients with a progression of fibrinogen depletion.

Telephone triage service use is associated with better outcomes among patients with cerebrovascular diseases: a propensity score analysis using population-based data.

Introduction: The telephone triage service is an emergency medical system through which citizens consult telephone triage nurses regarding illness, and the nurses determine the urgency and need for an ambulance. Despite being introduced in several countries, its impact on emergency patients has not been reported. We aimed to determine the effect of the telephone triage service on the outcomes of hospitalized patients diagnosed with cerebrovascular disease upon arrival after being transported by an ambulance. Methods: This retrospective study included patients with cerebrovascular disease who were transported by ambulance between January 2016 and December 2019. The primary outcome was discharge to home by day 21 of hospitalization. A total of 344 patients who used the telephone triage service were propensity score-matched to 344 patients who directly called for an ambulance. Results: Telephone triage service use was associated with discharge to home by hospital day 21 (crude odd ratio: 1.8; 95% confidence interval: 1.3-2.4) and was not significantly associated with survival on hospital day 21 in multivariate regression analysis. Conclusion: The prognoses of cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage depend on the time from symptom onset to treatment. Telephone triage services may allow patients to receive treatment more rapidly than traditional ambulance requests, resulting in improved patient outcomes. The findings of this study suggest that the use of telephone triage services is associated with improved outcomes in patients with cerebrovascular disease and indicate that the costs for medical expenses and disability may be greatly reduced in an aging society.

Zinc and iron dynamics in human islet amyloid polypeptide-induced diabetes mouse model.

Metal homeostasis is tightly regulated in cells and organisms, and its disturbance is frequently observed in some diseases such as neurodegenerative diseases and metabolic disorders. Previous studies suggest that zinc and iron are necessary for the normal functions of pancreatic ß cells. However, the distribution of elements in normal conditions and the pathophysiological significance of dysregulated elements in the islet in diabetic conditions have remained unclear. In this study, to investigate the dynamics of elements in the pancreatic islets of a diabetic mouse model expressing human islet amyloid polypeptide (hIAPP): hIAPP transgenic (hIAPP-Tg) mice, we performed imaging analysis of elements using synchrotron scanning X-ray fluorescence microscopy and quantitative analysis of elements using inductively coupled plasma mass spectrometry. We found that in the islets, zinc significantly decreased in the early stage of diabetes, while iron gradually decreased concurrently with the increase in blood glucose levels of hIAPP-Tg mice. Notably, when zinc and/or iron were decreased in the islets of hIAPP-Tg mice, dysregulation of glucose-stimulated mitochondrial respiration was observed. Our findings may contribute to clarifying the roles of zinc and iron in islet functions under pathophysiological diabetic conditions.

PPARα activation partially drives NAFLD development in liver-specific Hnf4a-null mice.

HNF4α regulates various genes to maintain liver function. There have been reports linking HNF4α expression to the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. In this study, liver-specific Hnf4a-deficient mice (Hnf4aΔHep mice) developed hepatosteatosis and liver fibrosis, and they were found to have difficulty utilizing glucose. In Hnf4aΔHep mice, the expression of fatty acid oxidation-related genes, which are PPARα target genes, was increased in contrast to the decreased expression of PPARα, suggesting that Hnf4aΔHep mice take up more lipids in the liver instead of glucose. Furthermore, Hnf4aΔHep/Ppara-/- mice, which are simultaneously deficient in HNF4α and PPARα, showed improved hepatosteatosis and fibrosis. Increased C18:1 and C18:1/C18:0 ratio was observed in the livers of Hnf4aΔHep mice, and the transactivation of PPARα target gene was induced by C18:1. When the C18:1/C18:0 ratio was close to that of Hnf4aΔHep mouse liver, a significant increase in transactivation was observed. In addition, the expression of Pgc1a, a coactivator of PPARs, was increased, suggesting that elevated C18:1 and Pgc1a expression could contribute to PPARα activation in Hnf4aΔHep mice. These insights may contribute to the development of new diagnostic and therapeutic approaches for NAFLD by focusing on the HNF4α and PPARα signaling cascade.

Establishment of an enzyme-linked immunosorbent assay for mouse pancreatic polypeptide clarifies the regulatory mechanism of its secretion from pancreatic γ cells.

Pancreatic polypeptide (PP), secreted from γ cells of the islets of Langerhans, is a 36 amino-acid peptide encoded by the Ppy gene. Although previous studies have reported that PP causes a decrease in appetite, the molecular mechanism that regulates PP secretion has not been fully elucidated. Lack of understanding of the regulatory mechanism of PP secretion may be partially owing to the lack of assay systems that can specifically detect PP. We recently developed the mouse monoclonal antibody 23-2D3 that specifically recognizes PP. In the present study, we developed a sandwich enzyme-linked immunosorbent assay for the measurement of mouse PP, and directly monitored intracellular Ca2+ concentrations in Ppy-expressing cells from a newly developed reporter mouse. Using these systems, we identified agonists, such as carbachol and glucose-dependent insulinotropic polypeptide (GIP), which stimulate PP secretion. We further demonstrated that, unlike the case of GIP-induced insulin secretion from ß cells, there is a unique mechanism by which PP secretion is triggered by an increase in intracellular Ca2+ concentrations via voltage-dependent calcium channels even in low-glucose conditions.

Development of clinical phenotypes and biological profiles via proteomic analysis of trauma patients.

BACKGROUND: Trauma is a heterogeneous condition, and specific clinical phenotypes may identify target populations that could benefit from certain treatment strategies. In this retrospective study, we determined clinical phenotypes and identified new target populations of trauma patients and their treatment strategies. METHODS: We retrospectively analyzed datasets from the Japan Trauma Data Bank and determined trauma death clinical phenotypes using statistical machine learning techniques and evaluation of biological profiles. RESULTS: The analysis included 71,038 blunt trauma patients [median age, 63 (interquartile range [IQR], 40-78) years; 45,479 (64.0%) males; median Injury Severity Score, 13 (IQR, 9-20)], and the derivation and validation cohorts included 42,780 (60.2%) and 28,258 (39.8%) patients, respectively. Of eight derived phenotypes (D-1-D-8), D-8 (n = 2178) had the highest mortality (48.6%) with characteristic severely disturbed consciousness and was further divided into four phenotypes: D-8α, multiple trauma in the young (n = 464); D-8ß, head trauma with lower body temperature (n = 178); D-8γ, severe head injury in the elderly (n = 957); and D-8δ, multiple trauma, with higher predicted mortality than actual mortality (n = 579). Phenotype distributions were comparable in the validation cohort. Biological profile analysis of 90 trauma patients revealed that D-8 exhibited excessive inflammation, including enhanced acute inflammatory response, dysregulated complement activation pathways, and impaired coagulation, including downregulated coagulation and platelet degranulation pathways, compared with other phenotypes. CONCLUSIONS: We identified clinical phenotypes with high mortality, and the evaluation of the molecular pathogenesis underlying these clinical phenotypes suggests that lethal trauma may involve excessive inflammation and coagulation disorders.

Impact of Pelvic Fracture Sites on Fibrinogen Depletion in Patients with Blunt Trauma: A Single-Center Cohort Study.

BACKGROUND: We aimed to examine the association of pelvic fracture sites with the minimum fibrinogen level within 24 h after hospital arrival. METHODS: We conducted a single-center cohort study using health records review. We included patients with pelvic fractures transported by ambulance to a tertiary-care hospital from January 2012 to December 2018 and excluded those transported from other hospitals or aged younger than 16 years. The pelvic fracture was diagnosed and confirmed by trauma surgeons and/or radiologists. We classified the fracture sites of the pelvis as ilium, pubis, ischium, acetabulum, sacrum, sacroiliac joint diastasis, and pubic symphysis diastasis, and each side was counted separately except for pubic symphysis diastasis. We performed linear regression analysis to evaluate the association between pelvic fracture sites and the minimum fibrinogen level within 24 h of arrival. RESULTS: We analyzed 120 pelvic fracture patients. Their mean age was 47.3 years, and 69 (57.5%) patients were men. The median Injury Severity Score was 24, and in-hospital mortality was 10.8%. The mean minimum fibrinogen level within 24 h of arrival was 171.4 mg/dL. Among pelvic fracture sites, only sacrum fracture was statistically significantly associated with the minimum fibrinogen level within 24 h of arrival (estimate, -34.5; 95% CI, -58.6 to -10.4; p = 0.005). CONCLUSIONS: Fracture of the sacrum in patients with pelvic fracture was associated with lower minimum fibrinogen levels within 24 h of hospital arrival and the requirement of blood transfusion.

Telephone Triage for Emergency Patients Reduces Unnecessary Ambulance Use: A Propensity Score Analysis With Population-Based Data in Osaka City, Japan.

Background: Telephone triage service in emergency care has been introduced around the world, but the impact of this service on the emergency medical service (EMS) system has not been fully revealed. The aim of this study was to evaluate the effect of telephone triage service for emergency patients on decreasing unnecessary ambulance use by analysis with propensity score (PS) matching. Methods: This study was a retrospective observational study, and the study period was the 4 years from January 2016 to December 2019. We included cases for which ambulances were dispatched from the Osaka Municipal Fire Department (OMFD). The primary outcome of this study was unnecessary ambulance use. We calculated a PS by fitting a logistic regression model to adjust for 10 variables that existed before use of the telephone triage service. To ensure the robustness of this analysis, we used not only PS matching but also a multivariable logistic regression model and regression model with PS as a covariate. Results: This study included 868,548 cases, of which 8,828 (1.0%) used telephone triage services and 859,720 (99.0%) did not use this service. Use of the telephone triage service was inversely associated with the occurrence of unnecessary ambulance use in multivariate logistic regression model (adjusted OR 0.453, 95% CI 0.405-0.506) and multivariate logistic regression model with PS as a covariate (adjusted OR 0.514, 95% CI 0.460-0.574). In the PS matching model, we also revealed same results (crude OR 0.487, 95% CI 0.425-0.588). Conclusions: In this study, we were able to statistically evaluate the effectiveness of telephone triage service already in use by the public using the statistical method with PS. As a result, it was revealed that the use of a telephone triage service was associated with a lower proportion of unnecessary ambulance use in a metropolitan area of Japan.

Assessing the impact of the national traffic safety campaign: a nationwide cohort study in Japan.

OBJECTIVES: This study aimed to examine the difference in mortality from serious road traffic injuries during the National Traffic Safety Campaign compared with other periods and identify the common mechanisms of injury by age group in Japan. DESIGN: A retrospective review of Japan Trauma Data Bank (JTDB). SETTING: A total of 280 participating major emergency institutions across Japan. PARTICIPANTS: Patients with road traffic injuries registered in JTDB between 2004 and 2018 were recruited in the study. We included patients injured by traffic crashes during the National Traffic Safety Campaigns and controls using a double control method. The National Traffic Safety Campaign comprises 10 consecutive days in spring and fall (20 days in each year), and controls was the same calendar days 2 weeks before and after the days in the National Traffic Safety Campaigns (40 days in each year) to control for weekday, seasonal and yearly trends. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was in-hospital mortality. The secondary outcome was the incidences of severe traffic injury. RESULTS: Among 126 857 patients recorded as road traffic injuries in JTDB, we identified 6181 patients (21 cases per day) with injuries occurring during the National Traffic Safety Campaigns and 12 382 controls (21 cases per day). The overall in-hospital mortality was 11.4%. We did not observe a significant difference in in-hospital mortality between the groups (11.8% vs 11.1%) with an adjusted OR of 1.05 (95% CI 0.95 to 1.16). The most common mechanism of injury in each age group was bicycle crash among children, motorcycle crash among adults and pedestrian among the elderly. CONCLUSIONS: We found no change in the incidence of severe traffic injury or in-hospital mortality during the National Traffic Safety Campaign in Japan. Serious road trauma was high for bicycles among children, motorcycles among adults and pedestrian among the elderly.

Association of a telephone triage service for emergency patients with better outcome: a population-based study in Osaka City, Japan.

OBJECTIVE: Telephone triage service in emergency care has been introduced in many countries, and it is important to determine the effect of telephone triage service on the outcome of emergency patients. The aim of this study was to evaluate the effect of telephone triage service on the outcome of emergency patients using propensity score. METHODS DESIGN, SETTINGS, AND PARTICIPANTS: This was a retrospective study with a study period from January 2016 to December 2019. We included all patients transported by ambulances of the Osaka Municipal Fire Department during study period. EXPOSURE: Telephone triage service. OUTCOME MEASURES AND ANALYSIS: The main outcome of this study was unfavorable outcome following use of the telephone triage service. In this study, unfavorable outcome was defined as patients who were admitted, transferred, or died after care in the emergency department. Propensity scores were calculated using a logistic regression model with 12 variables that were present before the telephone triage service was used or were indicative of the patient's condition. Data analyses were not only propensity score matching but also a multivariable logistic regression model and regression model with propensity score as a covariate. MAIN RESULTS: The number of patients eligible for analyses was 707 474. Of these patients, 8008 (1.0%) used the telephone triage services and 699 466 patients (99.0%) did not use it. The number of patients with an unfavorable outcome was 407 568 (57.6%) in the total cohort. Of them, 2305 patients (28.8%) used the telephone triage service and 297 601 patients (42.5%) did not use it. For propensity score matching, 8008 patients were matched from each group. Use of the telephone triage service was inversely associated with unfavorable outcome in a multivariate logistic regression model with propensity score as a covariate [adjusted odds ratio (OR) 0.874; 95% confidence interval (CI), 0.831-0.919] and propensity score matching (crude OR, 0.875; 95% CI, 0.818-0.936). CONCLUSIONS: This study revealed that the use of the telephone triage service in Osaka city, Japan was associated with better outcomes of patients transported by ambulance.

Patient age affects sex-based differences in post-traumatic mortality: a national trauma registry study in Japan.

PURPOSE: Sex-based differences in post-traumatic mortality have been widely discussed for quite some time. We hypothesized that age-related pathophysiologic changes would affect sex-based differences in post-traumatic mortality and aimed to verify the hypothesis using a nationwide trauma registry in Japan. METHODS: This was a retrospective analysis of trauma patients registered in The Japanese Trauma Data Bank. We stratified the study population into the following three subsets based on age: (1) pediatric subset (age ≤ 14), (2) adult subset (age 15-50) and (3) senior adult subset (age ≥ 51). We evaluated both sex-based differences in mortality in each subset separately using multivariate logistic regression analysis and the two-way interaction effect for predicted survival between the continuous increase of age and the sexes using a nonlinear multivariate regression model. RESULTS: We included 122,819 trauma patients who fulfilled the inclusion criteria and classified them into the 3 subsets according to age. Male patients were more likely to die compared to female patients only in the senior adult subset (adjusted odds ratio: 1.26; 95% confidence interval: 1.18-1.36), whereas there were no statistically significant differences in the other two subsets. Furthermore, non-linear logistic regression analysis revealed that predicted survival probability in male patients decreased more sharply in accordance with the increase of age compared to that in female patients (p for interaction: 0.051). CONCLUSION: Age-related change in post-traumatic mortality was significantly different between males and females, and male patients had a relatively higher risk of death in the older population.

Characteristics and outcomes of pediatric blunt renal trauma: a nationwide cohort study in Japan.

PURPOSE: The aim of this study was to describe epidemiologic features of pediatric blunt renal trauma. METHODS: We performed a retrospective analysis using the Japan Trauma Data Bank over 15 years. We included patients younger than 18 years with blunt renal trauma. We analyzed temporal trends and variations across age groups in patient characteristics, intervention, and in-hospital mortality. We also assessed factors associated with in-hospital mortality. RESULTS: We identified 435 pediatric patients with blunt renal trauma. Their median age was 14 years and median Injury Severity Score (ISS) was 17. The most common mechanism of injury was traffic accident in all age groups. Nephrectomy was performed in 3.2%, and the overall in-hospital mortality was 4.6%, both of which showed decreasing trends. The most common mechanism of injury by age group was a pedestrian accident in infants/toddlers/preschoolers (43.5%), pedestrian accident in middle childhood (18.5%), bicycle accident in young teens (24.7%), and motorcycle accident in teenagers (41.2%). Sports-related injury was common in young teens (23.3%) and teenagers (15.2%). Factors such as ISS, shock, concomitant injury, and nephrectomy were associated with high in-hospital mortality. CONCLUSIONS: We described decreasing trends in nephrectomy and in-hospital mortality in pediatric blunt renal trauma and found traffic accident and sports-related injury were common in the pediatric population in Japan.

Association of Pre-Hospital Helicopter Transport with Reduced Mortality in Traumatic Brain Injury in Japan: A Nationwide Retrospective Cohort Study.

Patients with traumatic brain injury (TBI) are severely injured patients who require timely, efficient, and specialized care. The effectiveness of helicopter emergency medical services (HEMS) for patients with TBI remains unclear. This study aimed to compare the mortality of patients with TBI transported by HEMS and ground ambulance using propensity score-matching analysis, and to analyze the effects of HEMS in various subpopulations. We conducted a retrospective analysis of the Japan Trauma Data Bank. The study period was from January 2004 to December 2018. The participants were divided into two groups: the helicopter group (patients transported by HEMS) and ground group (patients transported by ground ambulance). The principal outcome was death at hospital discharge. In total, 58,532 patients were eligible for analysis (ground group, n = 54,820 [93.7%]; helicopter group, n = 3712 [6.3%]). Helicopter transport decreased patient mortality at hospital discharge (adjusted odds ratio [OR], 0.83; 95% confidence interval [CI], 0.74-0.92). In propensity score-matched patients, the proportion of deaths at hospital discharge was lower in the helicopter (18.76%) than in the ground (21.21%) group (crude OR, 0.86; 95% CI, 0.77-0.96). The mortality rate in the helicopter group was significantly reduced in many subpopulations, especially in cases of severe TBI with a decreased level of consciousness or higher Injury Severity Score (ISS; Japan Coma Scale score 2 [adjusted OR, 0.60; 95% CI, 0.45-0.80] and ISS ≥50 [adjusted OR, 0.69; 95% CI, 0.48-0.99]). Although the study design was non-randomized, our findings in patients with TBI showed that HEMS conferred a mortality benefit over ground ambulance.

Evaluation of urinary extravasation after non-operative management of traumatic renal injury: a multi-center retrospective study.

PURPOSE: Urinary extravasation is one of the major complications after non-operative management of traumatic renal injury and may lead to urinary tract infection and sepsis. The purpose of this study was to evaluate these factors in patients with traumatic renal injury. METHODS: This was a multi-center, retrospective, observational study performed at three tertiary referral hospitals in Osaka prefecture. We included patients with traumatic renal injury transported to the centers between January 2008 and December 2018. We excluded patients who either died or underwent nephrectomy within 24 h after admission. We investigated the occurrence of urinary extravasation and the related factors after traumatic renal injury using multivariable logistic regression analysis. RESULTS: In total, 146 patients were eligible for analysis. Their median age was 44 years and 68.5% were male. Their median Injury Severity Score was 17. Renal injuries were graded as American Association for Surgery of Trauma (AAST) grade I in 33 (22.6%), II in 27 (18.5%), III in 38 (26.0%), IV in 28 (19.2%), and V in 20 (13.7%) patients. Urinary extravasation was diagnosed in 26 patients (17.8%) and was statistically significantly associated with AAST grades IV-V (adjusted odds ratio, 33.8 [95% confidence interval 7.12-160], p < 0.001). CONCLUSION: We observed urinary extravasation in 17.8% of patients with non-operative management of traumatic renal injury and the diagnosed was made in mostly within 7 days after admission. In this study, the patients with AAST grade IV-V injury were associated with having urinary extravasation.

Effect of fluid administration on scene to traffic accident patients by EMS personnel: a propensity score-matched study using population-based ambulance records and nationwide trauma registry in Japan.

PURPOSE: The aim of this study was to assess the effect of fluid administration by emergency life-saving technicians (ELST) on the prognosis of traffic accident patients by using a propensity score (PS)-matching method. METHODS: The study included traffic accident patients registered in the JTDB database from January 2016 to December 2017. The main outcome was hospital mortality, and the secondary outcome was cardiopulmonary arrest on hospital arrival (CPAOA). To reduce potential confounding effects in the comparisons between two groups, we estimated a propensity score (PS) by fitting a logistic regression model that was adjusted for 17 variables before the implementation of fluid administration by ELST at the scene. RESULTS: During the study period, 10,908 traffic accident patients were registered in the JTDB database, and we included 3502 patients in this study. Of these patients, 142 were administered fluid by ELST and 3360 were not administered fluid by ELST. After PS matching, 141 patients were selected from each group. In the PS-matched model, fluid administration by ELST at the scene was not associated with discharge to death (crude OR: 0.859 [95% CI, 0.500-1.475]; p = 0.582). However, the fluid group showed statistically better outcome for CPAOA than the no fluid group in the multiple logistic regression model (adjusted OR: 0.231 [95% CI, 0.055-0.967]; p = 0.045). CONCLUSION: In this study, fluid administration to traffic accident patients by ELST was associated not with hospital mortality but with a lower proportion of CPAOA.

The Evaluation of Helicopter Emergency Medical Services With a Physician for Acute Myocardial Infarction in Japan: A Registry-Based Study of Prognosis and Time Reduction.

OBJECTIVE: The aim of this study was to compare the prognosis and time reduction between helicopter emergency medical services (HEMS) with a physician and ground emergency medical services (GEMS) in acute myocardial infarction (AMI) cases. METHODS: This is a registry-based study of the Japan Helicopter Emergency Medical Service Registry from April 1, 2015, to March 31, 2018. RESULTS: A total of 605 cases of AMI were registered in the HEMS group and 794 cases in the GEMS group. In the cases of non-cardiopulmonary arrest (CPA), the prognosis between HEMS and GEMS did not differ significantly. Regarding the road distance, for ranges of 20 to 40 km and > 40 km, the times from the call to the angiography room were significantly shorter with HEMS than GEMS (median 91 vs. 97 minutes, P = .036 and 101 vs. 132 minutes, P = .002, respectively). In cases of CPA, HEMS had a higher rate of return of spontaneous circulation than GEMS (55.3% vs. 36.8%, P = .038), but HEMS had a lower prognosis than GEMS (22.9% vs. 38.9%, P = .036). CONCLUSION: The present study suggested that HEMS had an advantage in reducing the time to angiography in AMI cases of non-CPA. In cases of CPA, HEMS increased the return of spontaneous circulation without improving the prognosis.

Characterisation of Ppy-lineage cells clarifies the functional heterogeneity of pancreatic beta cells in mice.

AIMS/HYPOTHESIS: Pancreatic polypeptide (PP) cells, which secrete PP (encoded by the Ppy gene), are a minor population of pancreatic endocrine cells. Although it has been reported that the loss of beta cell identity might be associated with beta-to-PP cell-fate conversion, at present, little is known regarding the characteristics of Ppy-lineage cells. METHODS: We used Ppy-Cre driver mice and a PP-specific monoclonal antibody to investigate the association between Ppy-lineage cells and beta cells. The molecular profiles of endocrine cells were investigated by single-cell transcriptome analysis and the glucose responsiveness of beta cells was assessed by Ca2+ imaging. Diabetic conditions were experimentally induced in mice by either streptozotocin or diphtheria toxin. RESULTS: Ppy-lineage cells were found to contribute to the four major types of endocrine cells, including beta cells. Ppy-lineage beta cells are a minor subpopulation, accounting for 12-15% of total beta cells, and are mostly (81.2%) localised at the islet periphery. Unbiased single-cell analysis with a Ppy-lineage tracer demonstrated that beta cells are composed of seven clusters, which are categorised into two groups (i.e. Ppy-lineage and non-Ppy-lineage beta cells). These subpopulations of beta cells demonstrated distinct characteristics regarding their functionality and gene expression profiles. Ppy-lineage beta cells had a reduced glucose-stimulated Ca2+ signalling response and were increased in number in experimental diabetes models. CONCLUSIONS/INTERPRETATION: Our results indicate that an unexpected degree of beta cell heterogeneity is defined by Ppy gene activation, providing valuable insight into the homeostatic regulation of pancreatic islets and future therapeutic strategies against diabetes. DATA AVAILABILITY: The single-cell RNA sequence (scRNA-seq) analysis datasets generated in this study have been deposited in the Gene Expression Omnibus (GEO) under the accession number GSE166164 ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE166164 ).

Analysis of clinical factors and reasons that influence the disposition of cryopreserved embryos in Japanese patients with infertility treated in our clinic.

AIM: To investigate the clinical factors and factors that affect the decisions regarding storage of cryopreserved embryos obtained using assisted reproductive technology. METHODS: Clinical characteristics affecting the decisions regarding cryopreserved embryos were analyzed in 5724 Japanese couples who underwent in vitro fertilization (IVF) or intra-cytoplasmic sperm insemination (ICSI) and embryo transfer over 4 years since April 2015 at our clinic. Statistical analysis was carried out using JMP software. RESULTS: The number of oocytes retrievals and embryos stored, outcomes and number of children, and age of the female patients and male partners were related to the decision-making regarding cryopreserved embryos. Childbearing and no wish for another child were the major reasons for discontinuing embryo storage. The number of oocytes retrievals and embryos in storage, age of the female patients, and sex of the child were independently associated with this decision-making in 2682 patients with a single child. Women with male children were more likely to choose discontinuation of embryo storage than those with female children. CONCLUSION: Already having a child and not wishing for further treatment due to age along with the presence of a male child affect the decision to continue or discontinue embryo storage in Japanese patients with infertility.

Factors associated with posttraumatic meningitis among traumatic head injury patients: a nationwide study in Japan.

PURPOSE: Posttraumatic meningitis is one of the severe complications that can result in increased mortality and longer hospital stay among trauma patients. Factors such as cerebrospinal fluid (CSF) fistula and basilar skull fracture are associated with posttraumatic meningitis. However, it remains unclear whether procedures such as burr hole surgery in the emergency department and decompressive craniectomy are associated with posttraumatic meningitis. The aim of this study was to assess factors associated with posttraumatic meningitis with a nationwide hospital-based trauma registry in Japan. METHODS: This was a retrospective observational study with a 12-year study period from January 2004 to December 2015. We included trauma patients registered in the Japanese Trauma Data Bank, whose head Abbreviated Injury Scale score was ≥ 3 in this study. The main endpoint was the occurrence of meningitis during hospitalization. Multivariable logistic regression analysis was used to assess independent parameters associated with posttraumatic meningitis such as CSF fistula, burr hole surgery in the emergency department, and decompressive craniectomy. RESULTS: Among 60,390 head injury patients with head AIS score 3 or more, 284 (0.5%) patients had posttraumatic meningitis. Factors associated with posttraumatic meningitis were burr hole surgery in the emergency department (adjusted odds ratio [AOR] 2.158 [95% confidence interval (CI) 1.401-3.325]), decompressive craniectomy (AOR 2.123 [95% CI 1.506-2.993]), external ventricular drainage (AOR 1.843 [95% CI, 1.157-2.935]), CSF leakage (AOR 3.328 [95% CI 2.205-5.022]), and basilar skull fracture (AOR 1.651 [95% CI 1.178-2.314]). CONCLUSIONS: In this population of trauma patients, burr hole surgery in the emergency department and decompressive craniectomy was associated with posttraumatic meningitis.