Changes in the Proportion of Each Cell Type After hiPSC-Derived Airway Epithelia Transplantation.

No radical treatment is available for the regeneration of dysfunction and defects in airway epithelia. Artificial tracheae made of polypropylene and collagen sponge were used in clinical studies to reconstitute tracheae after resection. For early epithelialization of the luminal surface of the artificial trachea, a model was established, that is, an artificial trachea covered with human-induced pluripotent stem cell-derived airway epithelial cells (hiPSC-AECs) was transplanted into a tracheal defect in an immunodeficient rat. Unlike the cell types of hiPSC-derived cells that are currently used in clinical studies, AECs maintain tissues by proliferation and differentiation of basal cells into various cell types that constitute AECs constantly. Therefore, post-transplantation, the proportion of each cell type, such as ciliated and goblet cells, may change; however, no studies have examined this possibility. In this study, using our hiPSC-AEC-transplanted rat model, we investigated changes in the proportion of each cell type in hiPSC-AECs pre-transplantation and post-transplantation. As a result, the proportion of each cell type changed post-transplantation. The proportion of ciliated, basal, and club cells increased, and the proportion of goblet cells decreased post-transplantation. In addition, the proportion of each cell type in engrafted hiPSC-AECs is more similar to the proportion of each cell type in normal proximal airway tissue than the proportion of each cell type pre-transplantation. The results of this study are useful for the development of therapeutic techniques using hiPSC-AEC transplantation.

Comparative Study of Immunodeficient Rat Strains in Engraftment of Human-Induced Pluripotent Stem Cell-Derived Airway Epithelia.

The airway epithelia (AE) play a role in the clearance of foreign substances through ciliary motility and mucus secreted. We developed an artificial trachea that is made of collagen sponges and polypropylene mesh for the regeneration of the tracheal defect, and it was used for a clinical study. Then, a model in which the luminal surface of an artificial trachea was covered with a human-induced pluripotent stem cell-derived AE (hiPSC-AE) was transplanted into the tracheal defect of nude rats to promote epithelialization. In the future, this model was expected to be applied to research on infectious diseases and drug discovery as a trachea-humanized rat model. However, at present, sufficient engraftment has not been achieved to evaluate functional recovery in transplanted cells. Therefore, this study focused on immunosuppression in recipient rats. Nude rats lack T cell function and are widely used for transplantation experiments; however, more severe immunosuppressed recipients are preferred for xenotransplantation. Several strains of immunodeficient rats were created as rats that exhibit more severe immunodeficiency until now. In this study, to establish a trachea-humanized rat model in which human AE function can be analyzed to improve engraftment efficiency, engraftment efficiency in nude rats and X-linked severe combined immunodeficiency (X-SCID) rats following hiPSC-AE transplantation was compared. In the analysis of the proportion of engrafted cells in total cells at the graft site, the engraftment efficiency of epithelial cells tended to be high in X-SCID rats, although no statistical difference was found between the two groups, whereas the engraftment efficiency of mesenchymal cells was higher in X-SCID rats. Furthermore, the number of immune cells that accumulated in the grafts showed that a pan T cell marker, that is, CD3-positive cells, did not differ between the two strains; however, CD45-positive cells and major histocompatibility complex (MHC) class II-positive cells significantly decreased in X-SCID rats. These results indicate that X-SCID rats are more useful for the transplantation of hiPSC-AE into the tracheae to generate trachea-humanized rat models.

Concurrent trastuzumab deruxtecan-induced interstitial lung disease and COVID-19 in the treatment of advanced breast cancer.

Patients with cancer are at an increased risk of developing coronavirus disease 2019 (COVID-19) infection. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) against epidermal growth factor receptor 2 (HER2)-positive cancer, known to cause drug-induced interstitial lung disease (DILD), including drug-induced pneumonitis. A 60-year-old woman with breast cancer developed a fever during treatment with T-DXd and was diagnosed with COVID-19. The fever persisted for approximately 3 weeks, and chest computed tomography showed multiple consolidations with bilateral peripheral predominance. Since the clinical course was atypical for COVID-19 due to the long duration of the fever and the CT pattern was frequently seen in T-DXd-induced ILD, the patient was diagnosed with T-DXd-induced ILD, following which, prednisolone was started, leading to improvement in the symptoms and fading of shadows. Even in patients suspected of COVID-19 pneumonia, physicians should consider the possibility of DILD, particularly in patients undergoing cancer treatment.

Laryngeal Cartilage Regeneration of Nude Rats by Transplantation of Mesenchymal Stem Cells Derived from Human-Induced Pluripotent Stem Cells.

Previous studies transplanted human-induced pluripotent stem cells (hiPSCs)-derived mesenchymal stem cells (iMSCs) into thyroid cartilage defect of X-liked severe combined immunodeficiency (X-SCID) rats and confirmed transplanted cell survival and cartilage regeneration. Thus, this study aimed to investigate the contribution of iMSC transplantation to thyroid cartilage regeneration of nude rats. iMSCs were induced from hiPSCs via a neural crest cell lineage. Then, clumps formed from an iMSC/extracellular matrix complex were transplanted into thyroid cartilage defects in nude rats. The larynx was removed and histological and immunohistochemical analyses were performed 4 or 8 weeks after the transplantation. Human nuclear antigen (HNA)-positive cells were observed in 11 of 12 (91.7%) rats, which indicated that transplanted iMSCs survived in thyroid cartilage defects in nude rats. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells in 8 of 12 rats (66.7%), which indicated cartilage-like regeneration. Cartilage-like regeneration in nude rats in this study was comparable to the previous report on X-SCID rats (HNA-positive cells were observed in all 14 rats and cartilage-like regeneration was observed in 10 of 14 rats). This result suggests that nude rats could be an alternative to X-SCID rats in thyroid cartilage regeneration experiments using iMSCs, and this nude rat cartilage transplantation model may develop cartilage regeneration research concerning fewer problems such as infection due to immunosuppression.

Physiologic 18F-FDG muscle uptake in severe COPD: Implications for accurate lung cancer staging.

Recognizing physiologic 18F-fluorodeoxyglucose (FDG) uptake in severe COPD is crucial to avoid mistaking it for lung cancer metastasis. Correlating 18F-FDG avid lesions with co-registered computed tomography is essential for accurate lung cancer staging and preventing unnecessary interventions.

Transient asymptomatic pulmonary opacities in a patient with MET exon 14 skipping non-small cell lung cancer: A case report.

Mesenchymal epithelial transition factor receptor (MET) tyrosine kinase inhibitors (MET-TKIs) have been approved for the treatment of non-small cell lung cancers with MET exon 14 skipping mutations. Transient asymptomatic pulmonary opacities (TAPOs) associated with epidermal growth factor receptor (EGFR)-TKIs have been reported. Here, we report a case wherein ground-glass opacities (GGOs) appeared during the course of treatment with tepotinib, a MET-TKI, but spontaneously resolved with drug withdrawal, after which treatment was resumed with a reduced dose. Although there have been no reports of TAPOs with MET-TKIs, the clinical and imaging findings of this case were consistent with TAPOs. For TAPOs occurring because of MET-TKI, the drug can be continued under careful observation even if GGOs appear.

A retrospective analysis of revision framework surgeries for unilateral vocal fold paralysis / Análise retrospectiva das cirurgias de revisão do arcabouço laríngeo para paralisia unilateral de prega vocal

Abstract Introduction Revision framework surgeries might be required for unilateral vocal fold paralyses. However, outcomes and indications of revision surgeries have not been adequately documented. For a better understanding of indications for the procedure and to help in achieving better vocal outcomes, we performed a retrospective chart review of patients who underwent revision framework surgeries for unilateral vocal fold paralysis. Objectives This study aimed to present clinical features of patients who underwent revision framework surgeries for the treatment of unilateral vocal fold paralysis. Methods Of the 149 framework surgeries performed between October 2004 and October 2019, 21 revision framework surgeries were performed in 19 patients. Self-assessments by patients using the voice handicap index-10 questionnaire, and objective aerodynamic and acoustic assessments performed pre- and post-operatively were analyzed using the Wilcoxon's signed-rank test for paired comparisons. Results Undercorrection was indicated as reasons for revision surgeries in all cases. The revision techniques included type I thyroplasty, type IV thyroplasty, and arytenoid adduction, and revision surgeries were completed without any severe complication in all cases. Pre- and post-operative voice handicap index-10 scores were obtained in 12 cases, and other parameters were evaluated in 18 cases. Significant improvements were observed in voice handicap index-10 scores, maximum phonation time, mean flow rate, Current/Direct Current ratio, and pitch perturbation quotient. Conclusion Undercorrection was observed in all patients who underwent revision framework surgeries for unilateral vocal fold paralysis, and the initial assessment and planning are thought to be important in order to avoid revision surgeries. Revision surgeries were performed safely in all cases, and significantly improved vocal outcomes were observed, even after multiple procedures. Revision surgery should be considered for patients with unsatisfactory vocal functions after primary framework surgeries for unilateral vocal fold paralysis.

Resumo Introdução As cirurgias de revisão do arcabouço laríngeo podem ser necessárias em casos de paralisia unilateral de prega vocal. Entretanto, os resultados e as indicações das cirurgias de revisão não têm sido documentados de forma adequada. Para melhor compreensão das indicações do procedimento e para auxiliar na obtenção de melhores resultados vocais, fizemos uma revisão retrospectiva dos prontuários de pacientes submetidos a cirurgias de revisão do arcabouço laríngeo em paralisia unilateral de prega vocal. Objetivos Apresentar as características clínicas de pacientes submetidos a cirurgias de revisão do arcabouço laríngeo para tratamento de paralisia unilateral de prega vocal. Método Das 149 cirurgias de revisão do arcabouço laríngeo feitas entre outubro de 2004 e outubro de 2019, 21 cirurgias de revisão do arcabouço laríngeo foram feitas em 19 pacientes. As autoavaliações feitas pelos pacientes com o questionário voice handicap index‐10 e avaliações aerodinâmicas e acústicas objetivas feitas no pré e pós‐operatório foram analisadas com o teste de postos sinalizados de Wilcoxon para comparações pareadas. Resultados A hipocorreção foi apontada como o motivo das cirurgias de revisão em todos os casos. As técnicas de revisão incluíram tireoplastia tipo I, tireoplastia tipo IV e adução de aritenoide. As cirurgias de revisão foram feitas sem qualquer complicação grave em todos os casos. Os escores do questionário voice handicap index‐10 pré e pós‐operatórios foram obtidos em 12 casos e outros parâmetros foram avaliados em 18 casos. Melhorias significativas foram observadas nos escores do questionário, no tempo máximo de fonação, taxa de fluxo médio, relação antes/depois e no quociente de perturbação do pitch. Conclusão Hipocorreção foi observada em todos os pacientes submetidos a cirurgias de revisão do arcabouço laríngeo para paralisia unilateral de prega vocal e a avaliação inicial e o planejamento são considerados importantes para evitar cirurgias de revisão. As cirurgias de revisão foram feitas com segurança em todos os casos e melhoria significativa dos resultados vocais foi observada mesmo após múltiplos procedimentos. A cirurgia de revisão deve ser considerada para pacientes com funções vocais insatisfatórias após cirurgia primária do arcabouço laríngeo para paralisia unilateral de prega vocal.

Clustering out-of-hospital cardiac arrest patients with non-shockable rhythm by machine learning latent class analysis.

Aim: We aimed to identify subphenotypes among patients with out-of-hospital cardiac arrest (OHCA) with initial non-shockable rhythm by applying machine learning latent class analysis and examining the associations between subphenotypes and neurological outcomes. Methods: This study was a retrospective analysis within a multi-institutional prospective observational cohort study of OHCA patients in Osaka, Japan (the CRITICAL study). The data of adult OHCA patients with medical causes and initial non-shockable rhythm presenting with OHCA between 2012 and 2016 were included in machine learning latent class analysis models, which identified subphenotypes, and patients who presented in 2017 were included in a dataset validating the subphenotypes. We investigated associations between subphenotypes and 30-day neurological outcomes. Results: Among the 12,594 patients in the CRITICAL study database, 4,849 were included in the dataset used to classify subphenotypes (median age: 75 years, 60.2% male), and 1,465 were included in the validation dataset (median age: 76 years, 59.0% male). Latent class analysis identified four subphenotypes. Odds ratios and 95% confidence intervals for a favorable 30-day neurological outcome among patients with these subphenotypes, using group 4 for comparison, were as follows; group 1, 0.01 (0.001-0.046); group 2, 0.097 (0.051-0.171); and group 3, 0.175 (0.073-0.358). Associations between subphenotypes and 30-day neurological outcomes were validated using the validation dataset. Conclusion: We identified four subphenotypes of OHCA patients with initial non-shockable rhythm. These patient subgroups presented with different characteristics associated with 30-day survival and neurological outcomes.

Transplantation of a human induced pluripotent stem cell-derived airway epithelial cell sheet into the middle ear of rats.

INTRODUCTION: Early postoperative regeneration of the middle ear mucosa is essential for the prevention of postoperative refractory otitis media and recurrent cholesteatoma. As a means for intractable otitis media management, we focused on human induced pluripotent stem cell (hiPSC)-derived airway epithelial cells (AECs), which have been used in upper airway mucosal regeneration and transplantation therapy. In this study, we transplanted hiPSC-derived AECs into the middle ear of immunodeficient rats. METHODS: Following the preparation of AEC sheets from hiPSCs, the bilateral middle ear mucosa of X-linked severe combined immunodeficient rats was scraped, and the AEC sheets were transplanted in the ears unilaterally. RESULTS: Human nuclear antigen (HNA)-positive ciliated cells were observed on the transplanted side of the middle ear cavity surface in three of six rats in the 1-week postoperative group and in three of eight rats in the 2-week postoperative group. No HNA-positive cells were found on the control side. The percentage of HNA-positive ciliated cells in the transplanted areas increased in the 2-week postoperative group compared with the 1-week group, suggesting survival of hiPSC-derived AECs. Additionally, HNA-positive ciliated cells were mainly located at sites where the original ciliated cells were localized. Immunohistochemical analysis showed that the transplanted AECs contained cytokeratin 5- and mucin 5AC-positive cells, indicating that both basal cells and goblet cells had regenerated within the middle ear cavity. CONCLUSIONS: The results of this study are an important first step in the establishment of a novel transplantation therapy for chronic otitis media.

A retrospective analysis of revision framework surgeries for unilateral vocal fold paralysis.

INTRODUCTION: Revision framework surgeries might be required for unilateral vocal fold paralyses. However, outcomes and indications of revision surgeries have not been adequately documented. For a better understanding of indications for the procedure and to help in achieving better vocal outcomes, we performed a retrospective chart review of patients who underwent revision framework surgeries for unilateral vocal fold paralysis. OBJECTIVES: This study aimed to present clinical features of patients who underwent revision framework surgeries for the treatment of unilateral vocal fold paralysis. METHODS: Of the 149 framework surgeries performed between October 2004 and October 2019, 21 revision framework surgeries were performed in 19 patients. Self-assessments by patients using the voice handicap index-10 questionnaire, and objective aerodynamic and acoustic assessments performed pre- and post-operatively were analyzed using the Wilcoxon's signed-rank test for paired comparisons. RESULTS: Undercorrection was indicated as reasons for revision surgeries in all cases. The revision techniques included type I thyroplasty, type IV thyroplasty, and arytenoid adduction, and revision surgeries were completed without any severe complication in all cases. Pre- and post-operative voice handicap index-10 scores were obtained in 12 cases, and other parameters were evaluated in 18 cases. Significant improvements were observed in voice handicap index-10 scores, maximum phonation time, mean flow rate, Current/Direct Current ratio, and pitch perturbation quotient. CONCLUSION: Undercorrection was observed in all patients who underwent revision framework surgeries for unilateral vocal fold paralysis, and the initial assessment and planning are thought to be important in order to avoid revision surgeries. Revision surgeries were performed safely in all cases, and significantly improved vocal outcomes were observed, even after multiple procedures. Revision surgery should be considered for patients with unsatisfactory vocal functions after primary framework surgeries for unilateral vocal fold paralysis.

Transplantation of Human Induced Pluripotent Stem Cell-Derived Airway Cells on Vitrigel Membrane into Rat Nasal Cavity.

The nasal mucosa functions as a frontline biological defense against various foreign substances and pathogens. Maintaining homeostasis of the nasal epithelium is necessary to promote good health. Nasal epithelia are constantly replaced under normal conditions. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Since there is no treatment for this underlying condition, extrinsic manipulation is necessary to recover and maintain nasal epithelia in cases of hereditary diseases. In this study, we explored the use of airway epithelial cells (AECs), including multiciliated airway cells, derived from human induced pluripotent stem cells (iPSCs) on porcine atelocollagen vitrigel membranes, as a candidate of a therapeutic method for irreversible nasal epithelial disorders. To confirm the regenerative capacity of iPSC-derived AECs, we transplanted them into nasal cavities of nude rats. Although the transplanted cells were found within cysts isolated from the recipient nasal respiratory epithelia, they survived in some rats. Furthermore, the surviving cells were composed of multiple cell types similar to the human airway epithelia. The results could contribute to the development of novel transplantation-related technologies for the treatment of severe irreversible nasal epithelial disorders. Impact Statement Nasal respiratory epithelia are important for the functions of nasal cavity, including humidifying the air and filtering various toxic substances. However, hereditary diseases, including primary ciliary dyskinesia and cystic fibrosis, can result in intractable dysfunction of the nasal mucosa. Our novel method to transplant airway epithelial cells derived from human induced pluripotent stem cells will be a candidate method to replace malfunctioned nasal respiratory epithelia in such a situation. To secure our method's safety, we used porcine atelocollagen vitrigel membranes, which prevent the immune response and bovine spongiform encephalopathy, as a scaffold.

In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells.

The laryngotracheal cartilage is a cardinal framework for the maintenance of the airway for breathing, which occasionally requires reconstruction. Because hyaline cartilage has a poor intrinsic regenerative ability, various regenerative approaches have been attempted to regenerate laryngotracheal cartilage. The use of autologous mesenchymal stem cells (MSCs) for cartilage regeneration has been widely investigated. However, long-term culture may limit proliferative capacity. Human-induced pluripotent stem cell-derived MSCs (iMSCs) can circumvent this problem due to their unlimited proliferative capacity. This study aimed to investigate the efficacy of iMSCs in the regeneration of thyroid cartilage in immunodeficient rats. Herein, we induced iMSCs through neural crest cell intermediates. For the relevance to prospective future clinical application, induction was conducted under xeno-free/serum-free conditions. Then, clumps fabricated from an iMSC/extracellular matrix complex (C-iMSC) were transplanted into thyroid cartilage defects in immunodeficient rats. Histological examinations revealed cartilage-like regenerated tissue and human nuclear antigen (HNA)-positive surviving transplanted cells in the regenerated lesion. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells. These results indicated that the transplanted C-iMSCs promoted thyroid cartilage regeneration and some of the iMSCs differentiated into chondrogenic lineage cells. Induced MSCs may be a promising candidate cell therapy for human laryngotracheal reconstruction.

Optimal extracorporeal cardiopulmonary resuscitation inclusion criteria for favorable neurological outcomes: a single-center retrospective analysis.

AIM: Although age ≤75 years, witnessed arrest, shockable initial cardiac rhythm, and short cardiac arrest duration are commonly cited inclusion criteria for extracorporeal cardiopulmonary resuscitation (ECPR), these criteria are not well-established, and ECPR outcomes remain poor. We aimed to evaluate whether the aforementioned inclusion criteria are appropriate for ECPR, and estimate the improvements in prognoses associated with their fulfillment. METHODS: Between October 2009 and December 2017, we retrospectively examined consecutive out-of-hospital cardiac arrest patients who were admitted to our hospital and received ECPR. We established four ECPR inclusion criteria: age ≤75 years, witnessed arrest, shockable initial cardiac rhythm, and call-to-hospital arrival time ≤45 min, and also evaluated the relationship between these criteria and patient outcomes. RESULTS: During the study period, 1,677 out-of-hospital cardiac arrest patients were admitted to our hospital, and 156 (9%) with ECPR were examined. The proportion of favorable neurological outcomes was 15% (24/156). However, when the study population was limited to individuals who fulfilled all four criteria, 27% (15/55) had favorable neurological outcomes; only one patient had favorable outcomes when two or more criteria were fulfilled. There was a significant positive linear correlation between the proportion of cases with favorable neurological outcomes and fulfillment of the four criteria (P = 0.005, r = 0.975). CONCLUSION: Fulfillment of at least three of the aforementioned criteria could yield improved ECPR outcomes.

Recurrent laryngeal nerve regeneration using a self-assembling peptide hydrogel.

OBJECTIVES/HYPOTHESIS: To regenerate defected recurrent laryngeal nerves (RLNs), various methods have been developed. However, no consistently effective treatments are currently available because of their insufficient functional recovery. RADA16-I, a self-assembling peptide used clinically as a hemostat, reportedly supports neurite outgrowth and functional synapse formation in vitro. The purpose of this study was to investigate the effect of RADA16-I hydrogels on transected RLNs in rats. STUDY DESIGN: Animal experiments with controls. METHODS: Fifteen adult rats were divided into the following three groups: RADA16-I (+), RADA16-I (-), and neurectomy. A 6-mm gap of the left RLN was bridged using an 8-mm silicone tube in the RADA16-I (-) and RADA16-I (+) groups. Subsequently, RADA16-I hydrogel was injected into the tube in the RADA16-I (+) group. The surgical incisions were closed without any further treatment in the neurectomy group. After 8 weeks, laryngoscopy and electrophysiological and histological examinations were performed to evaluate the effect of RADA16-I on nerve regeneration and thyroarytenoid muscle atrophy. RESULTS: Although most rats in the three groups exhibited no improvements of their vocal fold movement, partial recovery was observed in one rat in the RADA16-I (+) group. The neurofilament-positive areas and the number of myelinated nerves in the RADA16-I (+) group were significantly higher than in the RADA16-I (-) group. The area of the left thyroarytenoid muscle in the RADA16-I (+) group was significantly larger than that of the neurectomy group. CONCLUSIONS: Our results suggested that RADA16-I hydrogel was effective for RLN regeneration. LEVEL OF EVIDENCE: NA Laryngoscope, 130:2420-2427, 2020.

Combined transoral-transhyoid endoscopic approach for hypopharyngeal cancer.

Endoscopic transoral surgery for hypopharyngeal cancer is an effective treatment option to avoid invasive open surgery or chemoradiation. Here we describe the case of a 66-year-old patient with cT2N0M0 pyriform sinus cancer whom we treated using a transoral-transhyoid endoscopic approach. Using this approach, a transhyoid route was created in addition to the transoral route and used to extirpate the tumor. En bloc resection of the tumor was completed without difficulty. A combined transoral-transhyoid approach is a useful surgical option for treatment of selected patients with hypopharyngeal cancer. This technique is straightforward to perform and can be used as a backup technique in endoscopic transoral surgery. Also, more complicated lesions can be resected by this approach than by a single-route transoral approach.

Pulmonary Tumor Thrombotic Microangiopathy Caused by a Parotid Tumor: Early Antemortem Diagnosis and Long-term Survival.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a high-mortality disease that is difficult to diagnose clinically. Our patient was an 80-year-old woman who came to us due to symptoms of increasing dyspnea. A clinical evaluation showed that she had hypoxemia and pulmonary arterial hypertension without any abnormalities in the major pulmonary arteries, bronchi, or alveoli. A lung perfusion scan showed multiple wedge-shaped perfusion defects. Further examination revealed adenocarcinoma in her right parotid gland with metastasis to the submandibular lymph nodes. We diagnosed her to have PTTM caused by a parotid tumor. The patient survived for 11 months with chemotherapy. An early antemortem diagnosis by minimally invasive examinations will help PTTM patients to survive longer.

Epidemiology and outcome of adult out-of-hospital cardiac arrest of non-cardiac origin in Osaka: a population-based study.

OBJECTIVES: To evaluate epidemiological characteristics of out-of-hospital cardiac arrests (OHCAs) by detailed non-cardiac cause and factors associated with the outcomes after OHCAs of non-cardiac origin. DESIGN: A prospective, population-based observational study. SETTING: The Utstein Osaka Project. PARTICIPANTS: 14,164 adult patients aged ≥20 years old with OHCAs due to non-cardiac origin who were resuscitated by emergency-medical-service personnel or bystanders, and then were transported to medical institutions from January 2005 to December 2011. PRIMARY OUTCOME MEASURES: One-month survival after OHCA. Multiple logistic regression analysis was used to assess factors that were potentially associated with the outcome. RESULTS: During the study period, the 1-month survival rate was 5.3% (755/14,164). The proportion of 1-month survival was 6.2% (510/8239) in external causes, 6.5% (94/1148) in respiratory diseases, 0.8% (11/1309) in malignant tumours, 4.9% (55/1114) in strokes and 4.1% (85/2054) in others. As for external causes, the proportion of 1-month survival was 14.3% (382/2670) in asphyxia, 4.2% (84/1999) in hanging, 0.7% (9/1300) in fall, 1.1% (12/1062) in drowning, 1.6% (12/765) in traffic injury, 3.7% (7/187) in drug overuse and 1.6% (4/256) in unclassified external causes. In a multivariate analysis, adults aged <65 years old with arrests witnessed by bystanders, with normal activities of daily living before the arrests, having ventricular fibrillation arrests, having arrests in public places, intravenous fluid levels and early Emergency Medical Service response time were significant predictors for 1-month outcome after OHCAs of non-cardiac origin. The proportion of 1-month survival of all OHCAs of non-cardiac origin did not significantly increase (from 4.3% (86/2023) in 2005 to 4.9% (105/2126) in 2011) and the adjusted OR for one-increment of year was 1.01 (95% CI 0.97 to 1.06). CONCLUSIONS: From a large OHCA registry in Osaka, we demonstrated that 1-month survival after OHCAs of non-cardiac origin was poor and stable.

Actual treatments for out-of-hospital ventricular fibrillation at critical care medical centers in Osaka: a pilot descriptive study.

AIM: Although advanced treatments are provided to improve outcomes after out-of-hospital ventricular fibrillation, including shock-resistant ventricular fibrillation, the actual treatments in clinical settings have been insufficiently investigated. The aim of the current study is to describe the actual treatments carried out for out-of-hospital ventricular fibrillation patients, including shock-resistant ventricular fibrillation patients, at critical care medical centers. METHODS: We registered consecutive adult patients suffering bystander-witnessed out-of-hospital cardiac arrest of cardiac origin, for whom resuscitation was attempted by emergency medical service personnel, who had ventricular fibrillation as an initial rhythm, and who were transported to critical care medical centers in Osaka from March 2008 to December 2008. This study merged data on treatments after transportation, collected from 11 critical care medical centers in Osaka with the prehospital Utstein-style database. RESULTS: During the study period, there were 260 bystander-witnessed ventricular fibrillation arrests of cardiac origin. Of them, 252 received defibrillations before hospital arrival, 112 (44.4%) were transported to critical care medical centers, and 35 had shock-resistant ventricular fibrillation. At the critical care medical centers, 54% (19/35), 40% (14/35), and 46% (16/35) of shock-resistant ventricular fibrillation patients were treated with extracorporeal life support, percutaneous coronary interventions, and therapeutic hypothermia, respectively, but their treatments differed among institutions. Some patients with prolonged arrest without prehospital return of spontaneous circulation who received advanced treatments had neurologically favorable survival, whereas approximately two-thirds of shock-resistant ventricular fibrillation patients with advanced treatments did not. CONCLUSION: This pilot descriptive study suggested that actual treatments for prehospital ventricular fibrillation patients differed between critical care medical centers. Further studies are warranted to evaluate the effectiveness of in-hospital advanced treatments for ventricular fibrillation including shock-resistant ventricular fibrillation.

Verification of airway management during cardiac arrest: a manikin-based observational study.

INTRODUCTION: The study aimed to clarify the difficulties concerning insertion of advanced airway devices during cardiac arrest. METHOD: In an observational study using manikins, we examined the airway management techniques of 19 teams at the Osaka Senri medical rally. For ex-post verification, we recorded chest compression and ventilation using the Resusci Anne Advanced Skill Trainer (Laerdal, Norway) and recorded actions of the teams using a video camera. RESULTS: Only a small proportion of teams did not adopt advanced airway management (4 teams, 21.1%). Thirteen teams selected tracheal intubation. None showed chest compression interruptions during intubation manipulation, and the median duration of chest compression interruption during confirmation of postintubation was 6.4 seconds. The median duration of ventilation interruption during intubation was 45.5 seconds. When teams were evaluated for the duration of direct laryngoscopy, that is, so-called duration of intubation, the median duration was 19 seconds, which constituted a large underestimate compared with the duration of ventilation interruption. This represents an underestimation of about 27 seconds. We considered the issues to be identified for shortening the duration of ventilation interruption. CONCLUSION: From this study, it is clear that the strategy of Guideline 2005 that was designed to minimize chest compression interruption has permeated deeply. The recommendation that the duration of intubation manipulation should not exceed 30 seconds has had various interpretations, but it is important to focus on the duration of ventilation interruption.