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ICUとCCU 45(9) 551-556 2021年9月感染源のコントロールは敗血症診療の柱である。一方、感染巣を明らかにするための画像診断も感染源コントロールのために等しく重要であることから、敗血症診療ガイドライン2020では画像診断と感染源のコントロールが項目として統合された。画像診断では、疑われる各感染源に対してCT検査を中心に早期施行が推奨されるが、壊死性筋膜炎では外科的に直視すること、感染性心内膜炎ではエコー検査を検討する。各感染源に対するコントロールでは基本的に早期のドレナージ施行が原則とされるが、感染性膵壊死に関してはその限りではない。また、ドレナージの手法についても、低侵襲なドレナージから開始して患者の病態や臨床的な効果を見て侵襲の強度を上げる戦略が報告されるようになり、低侵襲アプローチを常に念頭に置いて治療を組み立てることが推奨される。(著者抄録)
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救急・集中治療 33(3) 1001-1004 2021年9月＜Point＞▼敗血症などの重症病態では、侵襲による過剰な生体反応が各種臓器障害を引き起こすことが知られている。▼過剰な生体反応の主役を担うのはサイトカインなどの炎症性メディエーターであり、外来微生物が産生するPAMPsや内因性物質であるDAMPsによってその産生が促される。▼炎症性メディエーターの中で、特にIL-6血中濃度は重症度や転帰と関連しており、臨床現場での指標として有用性が示唆されている。(著者抄録)
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日本集中治療医学会雑誌 28(Suppl.2) 207-207 2021年9月
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Journal of intensive care 9(1) 53-53 2021年8月25日The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.
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Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2021年8月8日OBJECTIVES: This study aimed to determine antibody responses in healthcare workers who receive the BNT162b2 mRNA COVID-19 vaccine and identify factors that predict the response. METHODS: We recruited healthcare workers receiving the BNT162b2 mRNA COVID-19 vaccine at the Chiba University Hospital COVID-19 Vaccine Center. Blood samples were obtained before the 1st dose and after the 2nd dose vaccination, and serum antibody titers were determined using Elecsys® Anti-SARS-CoV-2S, an electrochemiluminescence immunoassay. We established a model to identify the baseline factors predicting post-vaccine antibody titers using univariate and multivariate linear regression analyses. RESULTS: Two thousand fifteen individuals (median age 37-year-old, 64.3% female) were enrolled in this study, of which 10 had a history of COVID-19. Before vaccination, 21 participants (1.1%) had a detectable antibody titer (≥0.4 U/mL) with a median titer of 35.9 U/mL (interquartile range [IQR] 7.8 - 65.7). After vaccination, serum anti-SARS-CoV-2S antibodies (≥0.4 U/mL) were detected in all 1774 participants who received the 2nd dose with a median titer of 2060.0 U/mL (IQR 1250.0 - 2650.0). Immunosuppressive medication (p < 0.001), age (p < 0.001), time from 2nd dose to sample collection (p < 0.001), glucocorticoids (p = 0.020), and drinking alcohol (p = 0.037) were identified as factors predicting lower antibody titers after vaccination, whereas previous COVID-19 (p < 0.001), female (p < 0.001), time between 2 doses (p < 0.001), and medication for allergy (p = 0.024) were identified as factors predicting higher serum antibody titers. CONCLUSIONS: Our data demonstrate that healthcare workers universally have good antibody responses to the BNT162b2 mRNA COVID-19 vaccine. The predictive factors identified in our study may help optimize the vaccination strategy.
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Emergency medicine journal : EMJ 2021年7月21日BACKGROUND: The novel simplified out-of-hospital cardiac arrest (sOHCA) and simplified cardiac arrest hospital prognosis (sCAHP) scores used for prognostication of hospitalised patients have not been externally validated. Therefore, this study aimed to externally validate the sOHCA and sCAHP scores in a Japanese population. METHODS: We retrospectively analysed data from a prospectively maintained Japanese database (January 2012 to March 2013). We identified adult patients who had been resuscitated and hospitalised after intrinsic out-of-hospital cardiac arrest (OHCA) (n=2428, age ≥18 years). We validated the sOHCA and sCAHP scores with reference to the original scores in predicting 1-month unfavourable neurological outcomes (cerebral performance categories 3-5) based on the discrimination and calibration measures of area under the receiver operating characteristic curves (AUCs) and a Hosmer-Lemeshow goodness-of-fit test with a calibration plot, respectively. RESULTS: In total, 1985/2484 (82%) patients had a 1-month unfavourable neurological outcome. The original OHCA, sOHCA, original cardiac arrest hospital prognosis (CAHP) and sCAHP scores were available for 855/2428 (35%), 1359/2428 (56%), 1130/2428 (47%) and 1834/2428 (76%) patients, respectively. The AUCs of simplified scores did not differ significantly from those of the original scores, whereas the AUC of the sCAHP score was significantly higher than that of the sOHCA score (0.88 vs 0.81, p<0.001). The goodness of fit was poor in the sOHCA score (ν=8, χ2=19.1 and Hosmer-Lemeshow test: p=0.014) but not in the sCAHP score (ν=8, χ2=13.5 and Hosmer-Lemeshow test: p=0.10). CONCLUSION: The performances of the original and simplified OHCA and CAHP scores in predicting neurological outcomes in successfully resuscitated OHCA patients were acceptable. With the highest availability, similar discrimination and good calibration, the sCAHP score has promising potential for clinical implementation, although further validation studies to evaluate its clinical acceptance are necessary.
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Burns Open 5(3) 89-95 2021年7月
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Sensors (Basel, Switzerland) 21(13) 2021年6月27日Respiration is a key vital sign used to monitor human health status. Monitoring respiratory rate (RR) under non-contact is particularly important for providing appropriate pre-hospital care in emergencies. We propose an RR estimation system using thermal imaging cameras, which are increasingly being used in the medical field, such as recently during the COVID-19 pandemic. By measuring temperature changes during exhalation and inhalation, we aim to track the respiration of the subject in a supine or seated position in real-time without any physical contact. The proposed method automatically selects the respiration-related regions from the detected facial regions and estimates the respiration rate. Most existing methods rely on signals from nostrils and require close-up or high-resolution images, while our method only requires the facial region to be captured. Facial region is detected using YOLO v3, an object detection model based on deep learning. The detected facial region is divided into subregions. By calculating the respiratory likelihood of each segmented region using the newly proposed index, called the Respiratory Quality Index, the respiratory region is automatically selected and the RR is estimated. An evaluation of the proposed RR estimation method was conducted on seven subjects in their early twenties, with four 15 s measurements being taken. The results showed a mean absolute error of 0.66 bpm. The proposed method can be useful as an RR estimation method.
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IEICE Transactions on Fundamentals of Electronics, Communications and Computer Sciences 1(6) 887-896 2021年6月1日In medical fields, detecting traumatic bleedings has always been a difficult task due to the small size, low contrast of targets and large number of images. In this work we propose an automatic traumatic bleeding detection approach from contrast enhanced CT images via deep CNN networks, containing segmentation process and classification process. CT values of DICOM images are extracted and processed via three different window settings first. Small 3D patches are cropped from processed images and segmented by a 3D CNN network. Then segmentation results are converted to point cloud data format and classified by a classifier. The proposed pre-processing approach makes the segmentation network be able to detect small and low contrast targets and achieve a high sensitivity. The additional classification network solves the boundary problem and short-sighted problem generated during the segmentation process to further decrease false positives. The proposed approach is tested with 3 CT cases containing 37 bleeding regions. As a result, a total of 34 bleeding regions are correctly detected, the sensitivity reaches 91.89%. The average false positive number of test cases is 1678. 46.1% of false positive predictions are decreased after being classified. The proposed method is proved to be able to achieve a high sensitivity and be a reference of medical doctors.
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Shock (Augusta, Ga.) 55(6) 790-795 2021年6月1日BACKGROUND: Predicting multiple organ dysfunction (MOD) in the late phase of critical illnesses is essential. Cytokines are considered biomarkers that can predict clinical outcomes; however, their predictive value for late-phase MOD is unknown. This study aimed to identify the biomarker with the highest predictive value for late-phase MOD. METHODS: This observational study prospectively evaluated data on adult patients with systemic inflammatory response syndrome, those who presented to the emergency department or were admitted to intensive care units in five tertiary hospitals (n = 174). Seven blood biomarkers levels (interleukin-6 [IL-6], IL-8, IL-10, tumor-necrosis factor-α, white blood cells, C-reactive protein, and procalcitonin) were measured at three timepoints (days 0, 1, and 2). The area under the receiver operating characteristic curve (AUC) was analyzed to evaluate predictive values for MOD (primary outcome, MOD on day 7 [late-phase]; secondary outcome, MOD on day 3 [early-phase]). RESULTS: Of the measured 7 biomarkers, blood IL-6 levels on day 2 had the highest predictive value for MOD on day 7 using single timepoint data (AUC 0.825, 95% confidence interval [CI] 0.754-0.879). Using three timepoint biomarkers, blood IL-6 levels had the highest predictive value of MOD on day 7 (AUC 0.838, 95% CI 0.768-0.890). Blood IL-6 levels using three timepoint biomarkers had also the highest predictive value for MOD on day 3 (AUC 0.836, 95% CI 0.766-0.888). CONCLUSION: Of the measured biomarkers, blood IL-6 levels had the highest predictive value for MOD on days 3 and 7. Blood IL-6 levels predict early- and late-phase MOD in critically ill patients.
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The American journal of emergency medicine 43 290.e5-290.e7 2021年5月Some coronavirus disease 2019 (COVID-19) patients develop rapidly progressive acute respiratory distress syndrome and require veno-venous extracorporeal membrane oxygenation (V-V ECMO). A previous study recommended the transfer of ECMO patients to ECMO centers. However, because of the pandemic, a limited number of ECMO centers are available for patient transfer. The safe long-distance interhospital transport of these patients is a concern. To minimize transportation time, helicopter use is a suitable choice. We report the first case of a COVID-19 patient on V-V ECMO, transferred to our ECMO center by helicopter. A 45-year-old man with rheumatoid arthritis history, treated with immunosuppressants, presented with fever and sore throat. He was diagnosed with COVID-19 following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test result and was subsequently prescribed favipiravir. However, his respiratory failure progressively worsened. On day 10 of hospitalization at the previous hospital, he was intubated, and we received a request for ECMO transport on the next day. The ECMO team, who wore personal protective equipment (N95 respirators, gloves, gowns, and face shields), initiated V-V ECMO in the referring hospital and safely transported the patient by helicopter. The flight time was 7 min. He was admitted to the intensive care unit of our hospital and received tocilizumab. He was discharged on hospital day 31 with no significant sequelae. In this case report, we discuss important factors for the safe and appropriate interhospital transportation of COVID-19 patients on ECMO as well as staff and patient safety during helicopter transportation.
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World journal of emergency surgery : WJES 16(1) 19-19 2021年4月29日BACKGROUND: Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes. METHODS: A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016-2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO2 of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models. RESULTS: Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10-21) vs 23 (16-26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12-22) vs 23 (19-26), p = 0.004], but not among those intubated at the ED [18 (9-20) vs 15 (8-23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay. CONCLUSIONS: Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED. TRIAL REGISTRATION: UMIN-CTR, UMIN000019588 . Registered on November 15, 2015.
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Critical care explorations 3(4) e0387 2021年4月OBJECTIVES: Several inflammation markers have been reported to be associated with unfavorable clinical outcomes in critically ill patients. We aimed to elucidate whether serum interleukin-6 concentration considered with Sequential Organ Failure Assessment score can better predict mortality in critically ill patients. DESIGN: A prospective observational study. SETTING: Five university hospitals in 2016-2018. PATIENTS: Critically ill adult patients who met greater than or equal to two systemic inflammatory response syndrome criteria at admission were included, and those who died or were discharged within 48 hours were excluded. INTERVENTIONS: Inflammatory biomarkers including interleukin (interleukin)-6, -8, and -10; tumor necrosis factor-α; C-reactive protein; and procalcitonin were blindly measured daily for 3 days. Area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score at day 2 according to 28-day mortality was calculated as baseline. Combination models of Sequential Organ Failure Assessment score and additional biomarkers were developed using logistic regression, and area under the receiver operating characteristic curve calculated in each model was compared with the baseline. MEASUREMENTS AND MAIN RESULTS: Among 161 patients included in the study, 18 (11.2%) did not survive at day 28. Univariate analysis for each biomarker identified that the interleukin-6 (days 1-3), interleukin-8 (days 0-3), and interleukin-10 (days 1-3) were higher in nonsurvivors than in survivors. Analyses of 28-day mortality prediction by a single biomarker showed interleukin-6, -8, and -10 at days 1-3 had a significant discrimination power, and the interleukin-6 at day 3 had the highest area under the receiver operating characteristic curve (0.766 [0.656-0.876]). The baseline area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score predicting 28-day mortality was 0.776 (0.672-0.880). The combination model using additional interleukin-6 at day 3 had higher area under the receiver operating characteristic curve than baseline (area under the receiver operating characteristic curve = 0.844, area under the receiver operating characteristic curve improvement = 0.068 [0.002-0.133]), whereas other biomarkers did not improve accuracy in predicting 28-day mortality. CONCLUSIONS: Accuracy for 28-day mortality prediction was improved by adding serum interleukin-6 concentration to Sequential Organ Failure Assessment score.
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Scientific reports 11(1) 6313-6313 2021年3月18日Lactate clearance is affected by hepatic function. However, it is unclear whether the association between hepatic dysfunction and lactate clearance can act as a prognostic marker of clinical outcomes in patients with septic shock. We aimed to evaluate the association between lactate clearance and mortality in two cohorts of septic shock patient who had hepatic dysfunction based on their total serum bilirubin levels (TBIL). Lactate clearance at 24 h after the onset of septic shock was analyzed using two cohorts, sub-categorized into two groups based on TBIL: < 2 mg/dL and ≥ 2 mg/dL. In the derivation cohort, lactate clearance was lower in non-survivors than in survivors with TBIL ≥ 2 mg/dL, while there was no significant difference in lactate clearance between non-survivors and survivors with TBIL < 2 mg/dL. Multivariate logistic regression analysis revealed that increased lactate clearance was significantly associated with decreased 28-day mortality in the TBIL ≥ 2 mg/dL group (10% lactate clearance, adjusted odds ratio [OR]: 0.88, 95% confidence interval (CI): 0.80-0.97, P = 0.0075), Creatinine level ≥ 2 mg/dL group (adjusted OR: 0.88, 95% CI: 0.81-0.95, P = 0.00069) and APACHE II score ≥ 35 group (adjusted OR: 0.93, 95% CI: 0.87-0.98, P = 0.013). In the validation cohort, lactate clearance was lower in non-survivors than in survivors with TBIL ≥ 2 mg/dL, while no significant difference in lactate clearance was observed between non-survivors and survivors with TBIL < 2 mg/dL. Increased lactate clearance was significantly associated with decreased 28-day mortality in the TBIL ≥ 2 mg/dL group (10% lactate clearance, adjusted OR: 0.89, 95% CI: 0.83-0.96, P = 0.0038) and the association was just about significant in APACHE II score ≥ 35 group (adjusted OR: 0.86, 95% CI: 0.74-1.00, P = 0.051). In conclusion, increased lactate clearance in septic shock patients with hepatic dysfunction (TBIL ≥ 2 mg/dL) or high severity (APACHE II score ≥ 35) was associated with decreased 28-day mortality.
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Medicine 100(8) e24844 2021年2月26日ABSTRACT: This study aimed to identify prognostic factors for severe sepsis-related in-hospital mortality using the structural equation model (SEM) analysis with statistical causality. Sepsis data from the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma study (FORECAST), a multicenter cohort study, was used. Forty seven observed variables from the database were used to construct 4 latent variables. SEM analysis was performed on these latent variables to analyze the statistical causality among these data. This study evaluated whether the variables had an effect on in-hospital mortality. Overall, 1148 patients were enrolled. The SEM analysis showed that the 72-hour physical condition was the strongest latent variable affecting mortality, followed by physical condition before treatment. Furthermore, the 72-hour physical condition and the physical condition before treatment strongly influenced the Sequential Organ Failure Assessment (SOFA) score with path coefficients of 0.954 and 0.845, respectively. The SOFA score was the strongest variable that affected mortality after the onset of severe sepsis. The score remains the most robust prognostic factor and can facilitate appropriate policy development on care.
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Journal of intensive care 9(1) 21-21 2021年2月23日BACKGROUND: Cellular patterns in bronchoalveolar lavage fluid (BALF) are used to distinguish or rule out particular diseases in patients with acute respiratory failure (ARF). However, whether BALF cellular patterns can predict mortality or not is unknown. We test the hypothesis that BALF cellular patterns have predictive value for mortality in patients with ARF. METHODS: This was a retrospective single-center observational study conducted in a Japanese University Hospital. Consecutive patients (n = 78) with both pulmonary infiltrates and ARF who were examined by bronchoalveolar lavage (BAL) between April 2015 and May 2018 with at least 1 year of follow-up were analyzed. Primary analysis was receiver operating characteristic curve-area under the curve (ROC-AUC) analysis for 1-year mortality. RESULTS: Among the final sample size of 78 patients, survivors (n = 56) had significantly increased lymphocyte and eosinophil counts and decreased neutrophil counts in BALF compared with non-survivors (n = 22). Among the fractions, lymphocyte count was the most significantly different (30 [12-50] vs. 7.0 [2.9-13]%, P <0.0001). In the ROC curve analysis of the association of BALF lymphocytes with 1-year mortality, the AUC was 0.787 (P <0.0001, cut-off value [Youden index] 19.0%). Furthermore, ≥20% BALF lymphocytes were significantly associated with increased survival with adjustment for baseline imbalances (1-year adjusted hazard ratio, 0.0929; 95% confidence interval, 0.0147-0.323, P <0.0001; 90-day P =0.0012). Increased survival was significantly associated with ≥20% BALF lymphocytes in both interstitial lung disease (ILD) and non-ILD subgroups (P =0.0052 and P =0.0033, respectively). In secondary outcome analysis, patients with ≥20% BALF lymphocytes had significantly increased ventilator-free days, which represents less respiratory dysfunction than those with <20% BALF lymphocytes. CONCLUSIONS: In the patients with ARF, ≥20% lymphocytes in BALF was associated with significantly less ventilatory support, lower mortality at both 90-day and 1-year follow-ups.
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日本救急医学会雑誌 32(S1) S1-S411 2021年2月日本集中治療医学会と日本救急医学会は,合同の特別委員会を組織し,2016年に発表した日本版敗血症診療ガイドライン(J-SSCG)2016の改訂を行った。本ガイドライン(J-SSCG2020)の目的は,J-SSCG2016と同様に,敗血症・敗血症性ショックの診療において,医療従事者が患者の予後改善のために適切な判断を下す支援を行うことである。改訂に際し,一般臨床家だけでなく多職種医療者にも理解しやすく,かつ質の高いガイドラインとすることによって,広い普及を目指した。J-SSCG2016ではSSCG2016にない新しい領域[ICU-acquircd weakness(ICU-AW)とpost-intensive care syndrome(POCS),体温管理など]を取り上げたが,J-SSCG2020では新たに注目すべき4領域(Patient-and Family-Centered Care, sepsis treatment system,神経集中治療,ストレス潰瘍)を追加し,計22領域とした。重要な118の臨床課題(clinical question:CQ)をエビデンスの有無にかかわらず抽出した。これらのCQには,本邦で特に注目されているCQも含まれる。多領域にわたる大規模ガイドラインであることから,委員25名を中心に,多職種(看護師,理学療法士,臨床工学技士,薬剤師)および患者経験者も含めたワーキンググループメンバー,両学会の公募によるシステマティックレビューメンバーによる総勢226名の参加・協力を得た。また,中立的な立場で横断的に活躍するアカデミックガイドライン推進班をJ-SSCG2016に引き続き組織した。将来への橋渡しとなることを企図して,多くの若手医師をシステマティックレビューチーム・ワーキンググループに登用し,学会や施設の垣根を越えたネットワーク構築も進めた。作成工程においては,質の担保と作業過程の透明化を図るために様々な工夫を行い,パブリックコメント募集は計2回行った。推奨作成にはGRADE方式を取り入れ,修正Delphi法を用いて全委員の投票により推奨を決定した。結果,118CQに対する回答として,79個のGRADEによる推奨,5個のGPS(good practice statement),18個のエキスパートコンセンサス,27個のBQ(background question)の解説,および敗血症の定義と診断を示した。新たな試みとして,CQごとに診療フローなど時間軸に沿った視覚的情報を取り入れた。J-SSCG2020は,多職種が関わる国内外の敗血症診療の現場において,ベッドサイドで役立つガイドラインとして広く活用されることが期待される。なお,本ガイドラインは,日本集中治療医学会と日本救急医学会の両機関誌のガイドライン増刊号として同時掲載するものである。(著者抄録)
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Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27(2) 390-392 2021年2月 査読有りFavipiravir is an antiviral drug that is expected to have a therapeutic effect on SARS-CoV2 infection. Teratogenicity and hyperuricemia are known as the main side effects of favipiravir, but little is known about other side effects. This report describes a case of cholestatic liver injury induced by favipiravir. A 73-year-old Japanese with a history of alcoholic hepatitis was infected with SARS-CoV2. Drug therapy was instituted with lopinavir/ritonavir combined with interferon β-1b. However, his condition worsened despite additional support with continuous hemodiafiltration and veno-venous extracorporeal membrane oxygenation. We suspected complications of bacterial pneumonia and started favipiravir in addition to antimicrobial therapy. Favipiravir was administered at 6000 mg/day on the first day and 2400 mg/day for the second and subsequent days for 14 days. After the initiation of antibiotics, transaminase and total bilirubin were elevated, suggesting a transient cholestasic liver dysfunction. The liver dysfunction in this case may have been triggered by antibacterial treatment, and high dose of favipiravir may have promoted the deterioration of liver function. Monitoring of liver function is vital and close attention should be paid when using favipiravir at high doses or in patients with impaired liver function.
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The American Journal of Emergency Medicine 2021年2月
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International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 103 343-351 2021年2月BACKGROUND: There is no one-size-fits-all empiric antimicrobial therapy for sepsis because the pathogens vary according to the site of infection and have changed over time. Therefore, updating knowledge on the spectrum of pathogens is necessary for the rapid administration of appropriate antimicrobials. OBJECTIVE: The aim of this study was to elucidate the current spectrum of pathogens and its variation by site of infection in sepsis. METHODS: This was a prospective nationwide cohort study of consecutive adult patients with sepsis in 59 intensive care units in Japan. The spectrum of pathogens was evaluated in all patients and in subgroups by site of infection. Regression analyses were conducted to evaluate the associations between the pathogens and mortality. RESULTS: The study cohort comprised 1184 patients. The most common pathogen was Escherichia coli (21.5%), followed by Klebsiella pneumoniae (9.0%). However, the pattern varied widely by site of infection; for example, gram-positive bacteria were the dominant pathogen in bone/soft tissue infection (55.7%) and cardiovascular infection (52.6%), but were rarely identified in urinary tract infection (6.4%). In contrast, gram-negative bacteria were the predominant pathogens in abdominal infection (38.4%) and urinary tract infection (72.0%). The highest mortality of 47.5% was observed in patients infected with methicillin-resistant Staphylococcus aureus, which was significantly associated with an increased risk of death (odds ratio 1.88, 95% confidence interval 1.22-2.91). CONCLUSIONS: This study revealed the current spectrum of pathogens and its variation based on the site of infection, which is essential for empiric antimicrobial therapy against sepsis.
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Scientific reports 11(1) 1615-1615 2021年1月15日Current research regarding the association between body mass index (BMI) and altered clinical outcomes of sepsis in Asian populations is insufficient. We investigated the association between BMI and clinical outcomes using two Japanese cohorts of severe sepsis (derivation cohort, Chiba University Hospital, n = 614; validation cohort, multicenter cohort, n = 1561). Participants were categorized into the underweight (BMI < 18.5) and non-underweight (BMI ≥ 18.5) groups. The primary outcome was 28-day mortality. Univariate analysis of the derivation cohort indicated increased 28-day mortality trend in the underweight group compared to the non-underweight group (underweight 24.4% [20/82 cases] vs. non-underweight 16.0% [85/532 cases]; p = 0.060). In the primary analysis, multivariate analysis adjusted for baseline imbalance revealed that patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.031, adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.06-3.46). In a repeated analysis using a multicenter validation cohort (underweight n = 343, non-underweight n = 1218), patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.045, OR 1.40, 95% CI 1.00-1.97). In conclusion, patients with a BMI < 18.5 had a significantly increased 28-day mortality compared to those with a BMI ≥ 18.5 in Japanese cohorts with severe sepsis.
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Frontiers in medicine 8 767637-767637 2021年Background: Traumatic brain injury (TBI)-associated coagulopathy is a widely recognized risk factor for secondary brain damage and contributes to poor clinical outcomes. Various theories, including disseminated intravascular coagulation (DIC), have been proposed regarding its pathomechanisms; no consensus has been reached thus far. This study aimed to elucidate the pathophysiology of TBI-induced coagulopathy by comparing coagulofibrinolytic changes in isolated TBI (iTBI) to those in non-TBI, to determine the associated factors, and identify the clinical significance of DIC diagnosis in patients with iTBI. Methods: This secondary multicenter, prospective study assessed patients with severe trauma. iTBI was defined as Abbreviated Injury Scale (AIS) scores ≥4 in the head and neck, and ≤2 in other body parts. Non-TBI was defined as AIS scores ≥4 in single body parts other than the head and neck, and the absence of AIS scores ≥3 in any other trauma-affected parts. Specific biomarkers for thrombin and plasmin generation, anticoagulation, and fibrinolysis inhibition were measured at the presentation to the emergency department (0 h) and 3 h after arrival. Results: We analyzed 34 iTBI and 40 non-TBI patients. Baseline characteristics, transfusion requirements and in-hospital mortality did not significantly differ between groups. The changes in coagulation/fibrinolysis-related biomarkers were similar. Lactate levels in the iTBI group positively correlated with DIC scores (rho = -0.441, p = 0.017), but not with blood pressure (rho = -0.098, p = 0.614). Multiple logistic regression analyses revealed that the injury severity score was an independent predictor of DIC development in patients with iTBI (odds ratio = 1.237, p = 0.018). Patients with iTBI were further subdivided into two groups: DIC (n = 15) and non-DIC (n = 19) groups. Marked thrombin and plasmin generation were observed in all patients with iTBI, especially those with DIC. Patients with iTBI and DIC had higher requirements for massive transfusion and emergency surgery, and higher in-hospital mortality than those without DIC. Furthermore, DIC development significantly correlated with poor hospital survival; DIC scores at 0 h were predictive of in-hospital mortality. Conclusions: Coagulofibrinolytic changes in iTBI and non-TBI patients were identical, and consistent with the pathophysiology of DIC. DIC diagnosis in the early phase of TBI is key in predicting the outcomes of severe TBI.
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Frontiers in medicine 8 676277-676277 2021年Purpose: Portable chest radiographs are diagnostically indispensable in intensive care units (ICU). This study aimed to determine if the proposed machine learning technique increased in accuracy as the number of radiograph readings increased and if it was accurate in a clinical setting. Methods: Two independent data sets of portable chest radiographs (n = 380, a single Japanese hospital; n = 1,720, The National Institution of Health [NIH] ChestX-ray8 dataset) were analyzed. Each data set was divided training data and study data. Images were classified as atelectasis, pleural effusion, pneumonia, or no emergency. DenseNet-121, as a pre-trained deep convolutional neural network was used and ensemble learning was performed on the best-performing algorithms. Diagnostic accuracy and processing time were compared to those of ICU physicians. Results: In the single Japanese hospital data, the area under the curve (AUC) of diagnostic accuracy was 0.768. The area under the curve (AUC) of diagnostic accuracy significantly improved as the number of radiograph readings increased from 25 to 100% in the NIH data set. The AUC was higher than 0.9 for all categories toward the end of training with a large sample size. The time to complete 53 radiographs by machine learning was 70 times faster than the time taken by ICU physicians (9.66 s vs. 12 min). The diagnostic accuracy was higher by machine learning than by ICU physicians in most categories (atelectasis, AUC 0.744 vs. 0.555, P < 0.05; pleural effusion, 0.856 vs. 0.706, P < 0.01; pneumonia, 0.720 vs. 0.744, P = 0.88; no emergency, 0.751 vs. 0.698, P = 0.47). Conclusions: We developed an automatic detection system for portable chest radiographs in ICU setting; its performance was superior and quite faster than ICU physicians.
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日本救急医学会関東地方会雑誌 42(4) 83-86 2021年<p>千葉大学医学部附属病院の集中治療室に勤務する医療従事者を対象に, SARS-CoV-2感染症の抗体検査を実施した。PCR検査が陰性のICU医療従事者103名のうち, 2名 (1.9%) の医療従事者が抗体陽性であった (医師1名 ; IgM/IgG陽性, 看護師1名 ; IgG陽性) 。この研究結果から, COVID-19患者に対する診療行為を3カ月間経験しても, ICU医療従事者のSARS-CoV-2感染は少ないことが明らかになった。</p>
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PloS one 16(9) e0256977 2021年INTRODUCTION: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Although most patients with COVID-19 develop asymptomatic or mild disease, some patients develop severe disease. The effectiveness of various therapeutic agents, including antiviral drugs, steroids, and anti-inflammatories for COVID-19, have been being confirmed. The effect of administering steroids in early disease is unclear. This study therefore aimed to evaluate the effectiveness and risk of exacerbation of steroids administered preceding antiviral drugs in patients with COVID-19 pneumonia. METHODS: This retrospective, single-center, observational study included consecutive patients with COVID-19 between March 2020 and March 2021. Patients were divided into a steroids-first group and antiviral-drugs-first group. Mortality, duration of hospitalization, incidence rate and duration of intensive care unit (ICU) admission, intubation, and extracorporeal membrane oxygenation (ECMO) induction of the two groups were compared. RESULTS: A total of 258 patients were admitted during the study period. After excluding patients who received symptomatic treatment only, who were taking immunosuppressive drugs, or who were administered antiviral drugs only, 68 patients were included in the analysis, 16 in the steroids-first group and 52 in the antiviral-drugs-first group. The rate of intubation, ICU admission and ECMO induction were significantly higher in the steroids-first group than in the antiviral-drugs-first group (81.3% vs. 33.3, p<0.001, 75.0% vs. 29.4%, p = 0.001, and 31.3% vs. 7.8%, p = 0.017, respectively). Furthermore, patients who received steroids within ten days after starting antiviral drugs had significantly lower rates of ICU admission, intubation, and ECMO induction. (81.3% vs. 42.9% p = 0.011, 75.0% vs. 37.1% p = 0.012, and 31.3% vs. 8.6% p = 0.039, respectively). CONCLUSIONS: Administering steroids prior to antiviral drugs soon after symptom onset can aggravate disease severity. When administration of steroids is considered soon after symptom onset, it may be safer to initiate antiviral drugs first.
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日本救急医学会関東地方会雑誌 41(4) 383-387 2020年12月Rapid response system(RRS)が起動された入院患者において、入院診療科区分と心停止発症との関連について検討した。対象患者は314名、入院診療科は内科系122名、外科系153名、循環器系39名であった。3群間の背景因子の比較では、年齢、RRS起動以前のICU入室歴に有意差を認め、内科系で年齢が若く、外科系でICU入室歴の頻度が高かった。主要評価項目のmedical emergency team接触時の心停止は、単変量解析で3群間に有意な差を認め、循環器系で頻度が最も高かった。背景因子を調整した解析においても、循環器系の診療科区分は有意に心停止と関連していた。副次評価項目である重症例と28日死亡に関する解析では、診療科区分間で有意な差を認めなかった。循環器系診療科区分の入院患者は予期せぬ院内心停止発症のリスクが高いため、通常のRRSに加えて、さらなる予防策を講じる必要があると考えられた。
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Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs 23(4) 397-400 2020年12月Although several studies have reported on the clinical and epidemiological characteristics of the patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical course of the most severe cases requiring treatment in ICU have been insufficiently reported. A 73-year-old man traveling on a cruise ship with history of hypertension and dyslipidemia developed high fever, dyspnea and cough after 7 days of steroid treatment for sudden sensorineural hearing loss, and tested positive for SARS-CoV-2 in sputa polymerase chain reaction (PCR) examination. His respiratory function deteriorated despite treatments with lopinavir/ritonavir, oseltamivir, azithromycin and meropenem at a regional hospital. He was intubated and transferred to the ICU in the tertiary university hospital on day 10 (ICU day 1). Interferon beta-1b subcutaneous injection was initiated immediately to enhance anti-viral therapy, and favipiravir on ICU day 10 upon availability. Progression of organ dysfunctions necessitated inhalation of nitrogen oxide for respiratory dysfunction, noradrenaline for cardiovascular dysfunction and continuous renal replacement therapy for renal dysfunction. His blood samples PCR also tested positive for SARS-CoV-2, indicating viremia, concomitantly with elevated IL-6 levels. VV-ECMO was initiated after sudden exacerbation of respiratory dysfunction on ICU day 7 to maintain oxygenation. The sustained excessive inflammatory cytokines in the present case might have led to the exacerbation of the disease, requiring vigorous organ support therapies to allow for survival and recovery from the rapid progression of multiple organ dysfunctions and severe respiratory failure.
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BMC geriatrics 20(1) 485-485 2020年11月20日BACKGROUND: Frailty is associated with morbidity and mortality in patients admitted to intensive care units (ICUs). However, the characteristics of frail patients with suspected infection remain unclear. We aimed to investigate the characteristics and outcomes of frail patients with suspected infection in ICUs. METHODS: This is a secondary analysis of a multicenter cohort study, including 22 ICUs in Japan. Adult patients (aged ≥16 years) with newly suspected infection from December 2017 to May 2018 were included. We compared baseline patient characteristics and outcomes among three frailty groups based on the Clinical Frailty Scale (CFS) score: fit (score, 1-3), vulnerable (score, 4), and frail (score, 5-9). We conducted subgroup analysis of patients with sepsis defined as per Sepsis-3 criteria. We also produced Kaplan-Meier survival curves for 90-day survival. RESULTS: We enrolled 650 patients with suspected infection, including 599 (92.2%) patients with sepsis. Patients with a median CFS score of 3 (interquartile range [IQR] 3-5) were included: 337 (51.8%) were fit, 109 (16.8%) were vulnerable, and 204 (31.4%) were frail. The median patient age was 72 years (IQR 60-81). The Sequential Organ Failure Assessment scores for fit, vulnerable, and frail patients were 7 (IQR 4-10), 8 (IQR 5-11), and 7 (IQR 5-10), respectively (p = 0.59). The median body temperatures of fit, vulnerable, and frail patients were 37.5 °C (IQR 36.5 °C-38.5 °C), 37.5 °C (IQR 36.4 °C-38.6 °C), and 37.0 °C (IQR 36.3 °C-38.1 °C), respectively (p < 0.01). The median C-reactive protein levels of fit, vulnerable, and frail patients were 13.6 (IQR 4.6-24.5), 12.1 (IQR 3.9-24.9), 10.5 (IQR 3.0-21.0) mg/dL, respectively (p < 0.01). In-hospital mortality did not statistically differ among the patients according to frailty (p = 0.19). Kaplan-Meier survival curves showed little difference in the mortality rate during short-term follow-up. However, more vulnerable and frail patients died after 30-day than fit patients; this difference was not statistically significant (p = 0.25). Compared with the fit and vulnerable groups, the rate of home discharge was lower in the frail group. CONCLUSION: Frail and vulnerable patients with suspected infection tend to have poor disease outcomes. However, they did not show a statistically significant increase in the 90-day mortality risk.
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日本集中治療医学会雑誌 27(Suppl.) 284-284 2020年9月
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日本集中治療医学会雑誌 27(Suppl.) 550-550 2020年9月
MISC
165共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 2024年4月 - 2028年3月
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日本学術振興会 科学研究費助成事業 2024年4月 - 2027年3月
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日本学術振興会 科学研究費助成事業 2024年4月 - 2027年3月
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日本学術振興会 科学研究費助成事業 2024年4月 - 2027年3月
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日本学術振興会 科学研究費助成事業 2023年4月 - 2026年3月