記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Trials  

Background: The surgical techniques for treatment of chronic subdural hematoma (CSDH), a common neurosurgical condition, have been discussed in a lot of clinical literature. However, the recurrence proportion after CSDH surgery remains high, ranging from 10 to 20%. The standard surgical procedure for CSDH involves a craniostomy to evacuate the hematoma, but irrigating the hematoma cavity during the procedure is debatable. The authors hypothesized that the choice of irrigation fluid might be a key factor affecting the outcomes of surgery. This multicenter randomized controlled trial aims to investigate whether intraoperative irrigation using artificial cerebrospinal fluid (ACF) followed by the placement of a subdural drain would yield superior results compared to the placement of a subdural drain alone for CSDH. Methods: The study will be conducted across 19 neurosurgical departments in Japan. The 1186 eligible patients will be randomly allocated to two groups: irrigation using ACF or not. In either group, a subdural drain is to be placed for at least 12 h postoperatively. Similar to what was done in previous studies, we set the proportion of patients that meet the criteria for ipsilateral reoperation at 7% in the irrigation group and 12% in the non-irrigation group. The primary endpoint is the proportion of patients who meet the criteria for ipsilateral reoperation within 6 months of surgery (clinical worsening of symptoms and increased hematoma on imaging compared with the postoperative state). The secondary endpoints are the proportion of reoperations within 6 months, the proportion being stratified by preoperative hematoma architecture by computed tomography (CT) scan, neurological symptoms, patient condition, mortality at 6 months, complications associated with surgery, length of hospital stay from surgery to discharge, and time of the surgical procedure. Discussion: We present the study protocol for a multicenter randomized controlled trial to investigate our hypothesis that intraoperative irrigation with ACF reduces the recurrence proportion after the removal of chronic subdural hematomas compared with no irrigation. Trial registration: ClinicalTrials.gov jRCT1041220124. Registered on January 13, 2023.

DOI： 10.1186/s13063-023-07889-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Cardiothoracic and Vascular Anesthesia  

Objectives: To describe the current use and outcomes of temporary mechanical circulatory support (MCS) in patients with sepsis-associated cardiogenic shocks with and without acute myocardial infarction (AMI) in the United States. Design: Retrospective cohort study. Setting: The National Inpatient Sample database from 2017 to 2019. Participants: Adult patients with sepsis-associated cardiogenic shock with and without AMI. Interventions: Temporary MCSs, including intra-aortic balloon pump (IABP), percutaneous left ventricular assist device (pLVAD), and extracorporeal membrane oxygenation (ECMO). Measurements and Main Results: Multivariate logistic regression analyses adjusting for patient characteristics, organ failures, and socioeconomic status. Although the uses of IABP and pLVAD were associated with significantly lower odds of in-hospital mortality in patients with sepsis-associated cardiogenic shock (IABP: adjusted odds ratio [aOR] 0.57, 95% CI 0.44-0.73, p < .001; pLVAD: aOR 0.66, 95% CI 0.45-0.98, p = .037), ECMO was not (aOR 1.51, 95% CI 0.93-2.45, p = 0.096). In the subgroup with AMI, temporary MCSs were not associated with significantly lower or higher odds of in-hospital mortality. In the subgroup without AMI, IABP was associated with significantly lower odds of in-hospital mortality (aOR 0.43, 95% CI 0.28-0.65, p < 0.001). Conclusions: Although temporary MCS is deemed to be a feasible option in sepsis-associated cardiogenic shock, the selection of the right patients whose shock is driven mainly by cardiogenic shock rather than septic shock, as represented by low cardiac output and high systemic vascular resistance, plays a critical role in the feasibility of this approach in the absence of clinical trials.

DOI： 10.1053/j.jvca.2023.09.026

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Annals of Vascular Surgery  

Background: Patients with malignancy are at high risk of venous thromboembolism, and early diagnosis is important. The Khorana score is known as a risk assessment for cancer-related thrombosis during chemotherapy, but there are still few reports on its diagnostic potential, the optimal D-dimer cutoff values for indications other than chemotherapy and the use of the Khorana score in combination with D-dimers. In this study, we examined the clinical appropriateness of increasing the D-dimer cutoff value. Methods: We retrospectively studied 208 malignancies out of 556 patients who underwent lower extremity venous ultrasonography at our hospital over a 2-year period from January 2018 to December 2019. The optimal D-dimer cutoff value for predicting deep vein thrombosis (DVT) in patients with malignancy was calculated by the Youden index. The usefulness of the Khorana score alone and the model combining the Khorana score with D-dimer for predicting DVT diagnosis was compared using receiver operating characteristic analysis. Results: Of 208 eligible patients, 59 (28.4%) had confirmed DVT. The optimal D-dimer cutoff value for predicting DVT comorbidity in patients with malignancy was 3.96 μg/mL. When the new D-dimer cutoff value was set at 4.0 μg/mL, the odds ratio (OR) for DVT diagnosis was 4.23 (95% confidence interval (CI) 2.10–8.55, P < 0.001), which was higher than the OR of 1.33 (95% CI: 0.98–1.81, P = 0.064) for the Khorana score. The area under the curve for the Khorana score and D-dimer was 0.714, which was significantly higher than the 0.611 for the Khorana score alone, with the difference being significantly higher at 0.103 (P = 0.004, 95% CI: 0.033–0.173). Conclusions: The optimal D-dimer cutoff value for the diagnosis of DVT in patients with malignancy was 4.0 μg/mL. It was also suggested that the combination of the Khorana score with the D-dimer level was more accurate in diagnosing DVT than the Khorana score alone.

DOI： 10.1016/j.avsg.2023.06.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cancer Medicine  

Purpose: A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. Methods: Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m2 per day) on days 1–5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. Results: Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. Conclusion: Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

DOI： 10.1002/cam4.6974

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Neonatology  

Introduction: The effects of hydrocortisone (HDC) administration to extremely low birth weight (ELBW) infants on later development remain unclear. This study examined the association between HDC dosage during neonatal period and neurodevelopmental outcomes in ELBW infants. Methods: This study was a retrospective cohort study conducted in eight centers in Japan. The subjects of this study were ELBW infants born between April 2015 and March 2017. The association between postnatal total HDC dosage up to 36 weeks postmenstrual age and the developmental quotient (DQ) at 3 years of age was examined. Multiple linear regression evaluated the association, adjusting for weeks of gestation, birth weight, and the presence of bronchopulmonary dysplasia, late-onset circulatory collapse, intracranial hemorrhage, necrotizing enterocolitis, and sepsis. Results: This study included 218 ELBW infants, of whom 144 underwent a developmental test at 3 years of age. Simple linear regression analysis revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.65, 95% CI: -3.73, -1.57). Multiple linear regression analysis adjusted for the presence of bronchopulmonary dysplasia and late-onset circulatory collapse also revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.66, 95% CI: -3.89, -1.42). Conclusion: Higher total HDC dosage up to 36 weeks postmenstrual age in ELBW infants was associated with impaired neurodevelopmental outcomes. Although HDC is often needed in the treatment of ELBW infants, clinicians should be aware that an increased dose of HDC may be associated with impaired neurodevelopmental outcomes.

DOI： 10.1159/000534934

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Immunology  

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

DOI： 10.3389/fimmu.2024.1337070

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記述言語：英語   出版者・発行元：Nature and Science of Sleep  

Purpose: Both subjective and objective evaluations are essential for the treatment of insomnia. Lemborexant has been shown to be effective in the long-term based solely on a subjective basis, and no long-term objective measures have been evaluated under natural sleep conditions. Small, lightweight sleep electroencephalogram (EEG) monitor was used, instead of polysomnography, to objectively evaluate sleep at home 4 and 12 weeks after lemborexant treatment. Patients and Methods: Adults and elderly subjects with insomnia disorder, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were enrolled in this open-label, single-arm, single-center trial. Objective and subjective measures of sleep were prospectively assessed. Sleep disturbance, excessive sleepiness, and depressive symptoms were assessed using questionnaires. Results: A total of 45 subjects were screened, of which 33 were enrolled. Paired t-tests were conducted to evaluate changes in sleep variables and compared with the baseline; subjects showed significant improvements in objective sleep efficiency (SE) and subjective sleep parameters at weeks 4 and 12 following treatment with lemborexant. When baseline values were taken into account, a repeated-multivariate analysis of variance (MANOVA) revealed statistically significant changes in the objective measures. Sleep disturbance, excessive sleepiness, and depressive symptoms improved after three months of lemborexant treatment. Conclusion: Furthermore, lemborexant therapy improved nocturnal sleep, when measured objectively using sleep EEG monitoring at home, and improved daytime sleepiness and depressive symptoms in older adults with insomnia disorder.

DOI： 10.2147/NSS.S448871

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/SHK.0000000000002290

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Orthopaedic Research  

Bony impingement, especially in the anterior inferior iliac spine (AIIS) after total hip arthroplasty (THA), may cause dislocation. However, the influence of AIIS characteristics on bony impingement after THA is not fully understood. Thus, we aimed to determine the morphological characteristics of AIIS with developmental dysplasia of the hip (DDH) and primary osteoarthritis (pOA) and to evaluate its effect on range of motion (ROM) after THA. Hips from 130 patients who underwent THA, including pOA were analyzed. In total, we had 27 male and 27 female participants with pOA, and 38 male and 38 female participants with DDH. The horizontal distances of AIIS from teardrop (TD) were compared. In the computed tomography simulation, flexion ROM was measured, and its relationship to the distance between TD and AIIS was investigated. DDH had a more medial (male: DDH, 36.9 ± 5.8; pOA, 45.5 ± 6.1; p < 0.001) (female: DDH, 31.5 ± 10.0; pOA, 36.2 ± 4.7; p < 0.001) position of AIIS than pOA. In the male with pOA group, flexion ROM was significantly smaller than that in the other groups, and there was a correlation between flexion ROM and horizontal distances (r = −0.543; 95% confidence interval = −0.765 to −0.206; p = 0.003). AIIS position is a factor that limits ROM during flexion after THA, particularly in males. Further studies are required to develop surgical strategies for cases of impingement at the AIIS site after THA. Level of evidence: Ш, retrospective comparative study.

DOI： 10.1002/jor.25544

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記述言語：英語  

DOI： 10.1016/j.medine.2023.05.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Intensive Care Medicine  

Purpose: The prevalence and its impact on mortality of sepsis-induced cardiomyopathy (SICM) remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and prognosis of SICM. Materials and Methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Titles and abstracts were evaluated based on the following criteria: (1) published in English, (2) randomized controlled trials, cohort studies, or cross-sectional studies, (3) ≥ 18 years with sepsis, (4) reporting the prevalence and/or comparison of short-term mortality between those with and without SICM, defined as the new-onset reduction in left ventricular ejection fraction (LVEF) within 72 h on admission or from the diagnosis of sepsis. The random-effect model was used for all analyses. This meta-analysis was registered at PROSPERO (CDR42022332896). Results: Sixteen studies reported the prevalence of SICM and the pooled prevalence of SICM was 20% (95% confidence interval [CI], 16-25%; I2 = 89.9%, P < 0.01). Eleven studies reported short-term mortality and SICM was associated with significantly higher short-term mortality (The pooled odds ratio: 2.30, 95% CI, 1.43-3.69; I2 = 0%, P = 0.001). Conclusion: The prevalence of SICM was 20% in patients with sepsis, and the occurrence of SICM was associated with significantly higher short-term mortality.

DOI： 10.1177/08850666231180526

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASAIO Journal  

The effect and safety of bivalirudin compared with heparin in patients undergoing extracorporeal membrane oxygenation (ECMO) remains unclear. Therefore, we conducted a systematic review and meta-Analysis to compare the effectiveness and safety of heparin and bivalirudin in patients who underwent ECMO. We searched Embase, the Cochrane Central Register of Controlled Trials, and MEDLINE. Inclusion criteria included patients (1) undergoing ECMO and (2) receiving bivalirudin or heparin. We excluded studies where the majority of patients switched heparin to bivalirudin or vice versa during the clinical course. The primary outcome was short-Term mortality. We presented the results of all analyses with the use of random-effects models. Eleven studies reported short-Term mortality. The use of bivalirudin was associated with significantly lower short-Term mortality, compared with heparin (odds ratio: 0.71, 95% confidence interval, 0.55-0.92; p = 0.01, I2= 7%). In this meta-Analysis of observational studies, the use of bivalirudin was associated with significantly lower short-Term mortality, compared with heparin. Further prospective studies are warranted to clarify this finding.

DOI： 10.1097/MAT.0000000000001814

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Heliyon  

Background: Forged unsintered hydroxyapatite and poly L-lactic acid (F-u-HA/PLLA) screw is bioactivite, bioabsorbable, and radiopaque with high mechanical strength. Its efficacy has been previously demonstrated in the treatment of lateral humeral condylar, lateral tibial condylar, ankle, and patellar fractures. However, studies on its efficacy in treatment of calcaneal fractures is lacking. This study aimed to compare the postoperative results of F-u-HA/PLLA screw fixation and locking plate fixation for intra-articular calcaneal fractures. Methods: From January 2013 to December 2019, 47 closed intra-articular fractures treated with either F-u-HA/PLLA screws (group S, 18 feet in 17 patients) or locking plates (group P, 29 feet in 28 patients) in a single trauma center were retrospectively reviewed. The sinus tarsi approach was used in both groups. The time to bone union, step-off, varus deformity, Bohler's angle, and width and height of the calcaneus were assessed after surgery. Ankle joint range of motion (ROM) and postoperative complications were also assessed. Results: All fractures were successfully treated. The Kaplan-Meier curves of the two groups showed similar trends. The log-rank test showed no significant difference in the time to bone union between the two groups (p = 0.48). In the Cox proportional hazards model adjusted for preoperative width and Bohler's angle, the hazard ratio for bone union was not statistically significant (HR: 1.13, 95%CI: 0.50–2.56, p = 0.78). Other variables included step-off (group S: 2.0 vs group P: 2.2 mm, p = 0.84), varus deformity (2.0° vs. 3.0°, p = 0.7), Gissane's angle (103.5° vs 104.0°, p = 0.84), width (38.0 vs 34.8 mm, p = 0.12), height (42.1 vs 44.0 mm, p = 0.07), and ankle ROM degrees (dorsal flexion, 20.0° vs. 20.0°, p = 0.13; plantar flexion 40.0° vs 40.0°, p = 0.56), which were not significantly different between groups P and S. The Bohler's angle was smaller in group S than in group P (20.5° vs 27.0°, p < 0.01). No skin necrosis or infection was observed in either group. Conclusion: Postoperative results of F-u-HA/PLLA screw fixation using the sinus tarsi approach for intra-articular calcaneal fractures were as good as those of locking plate fixation.

DOI： 10.1016/j.heliyon.2023.e14046

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Orthopaedic Research  

Hyaluronan (HA) plays crucial roles in the maintenance of high-quality cartilage extracellular matrix. Several studies have reported the HA in synovial fluid in patients with osteoarthritis (OA), but few have described the changes of HA in articular cartilage of OA or idiopathic osteonecrosis of the femoral head (ONFH). KIAA1199 was recently reported to have strong hyaluronidase activity. The aim of this study was to clarify the HA metabolism in OA and ONFH, particularly the involvement of KIAA1199. Immunohistochemical analysis of KIAA1199 and HA deposition was performed for human OA (n = 10), ONFH (n = 10), and control cartilage (n = 7). The concentration and molecular weight (MW) of HA were determined by competitive HA ELISA and Chromatography, respectively. Regarding HA metabolism-related molecules, HAS1, HAS2, HAS3, HYAL1, HYAL2, and KIAA1199 gene expression was assessed by reverse transcriptase polymerase chain reaction. Histological analysis showed the overexpression of KIAA1199 in OA cartilage, which was accompanied by decreased hyaluronic acid binding protein (HABP) staining compared with ONFH and control. Little KIAA1199 expression was observed in cartilage at the collapsed area of ONFH, which was accompanied by a slight decrease in HABP staining. The messenger RNA (​​​​​mRNA) expression of HAS2 and KIAA1199 was upregulated in OA cartilage, while the mRNA expression of genes related to HA catabolism in ONFH cartilage showed mostly a downward trend. The MW of HA in OA cartilage increased while that in ONFH cartilage decreased. HA metabolism in ONFH is suggested to be generally indolent, and is activated in OA including high expression of KIAA1199. Interestingly, MW of HA in OA cartilage was not reduced.

DOI： 10.1002/jor.25364

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Artificial Organs  

Background: We evaluated the impact of a standardized driveline care strategy, including a subfascial-tunneling method and dressing protocol, on the incidence of driveline infection (DLI). Methods: DLI data from all HeartMate II (HMII) and HeartMate 3 (HM3) patients (including exchange devices) were retrospectively collected between 2013 and 2021. The driveline subfascial-tunneling method was altered in three steps (A: right direct; B: left triple, C: right triple), and the shower protocol was changed in two steps (A: with/without cover, B: with cover). Disinfection was individually tailored after changing the shower protocol. Complications associated with morbidity and mortality were evaluated for each modification. Results: During the study period, 80 devices were implanted (HMII, n = 54; HM3, n = 26). The 8-year incidence of DLI was 15% (n = 8) in HMII patients and 0% in HM3 patients (p = 0.039). DLI was not associated with hospital mortality. The modified dressing protocol and tunneling method was associated with a significantly better DLI incidence rate in comparison to the previous one: Protocol-A (n = 17), Protocol-B (n = 63), 35% vs 3% (p = 0.0009), Method-A (n = 13), Method-B (n = 42), Method-C (n = 25), 46% vs 5% vs 0% (p = 0.0001). The rete of freedom form DLI at 1, 2, and 3 years had also significant difference between groups: Protocol-A and Protocol-B, 80%, 54%, 54% vs 96%, 96%, 96%, respectively (p < 0.0001), Method-A, Method-B and Method-C, 76%, 44%, 44%, vs 94%, 94%, 94% vs 100%, 100%, respectively (p < 0.0001). Conclusions: A standardized triple driveline tunneling strategy and waterproof dressing protocol reduced driveline infection in HM3 patients to 0%.

DOI： 10.1111/aor.14426

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Circulation Journal  

Background: The effect of delayed ambulation on the outcome of coronary artery bypass grafting (CABG) remains to be clarified. Methods and Results: The long-term and in-hospital outcomes of 887 patients who underwent isolated CABG (455 off-pump cases, 135 urgent cases) were evaluated, with a focus on the timing of first ambulation. In-hospital mortality cases were excluded. Early ambulation (first ambulation within 3 days after operation) was achieved in 339 (38%) patients. In the multivariable logistic regression analysis, longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. Delayed ambulation was associated with a high incidence of postoperative complications, such as pneumonia, and stroke (P<0.01). Following discharge, 22.2% of patients experienced major cardiac events and 13.8% died during the follow-up period (median follow-up 60 months). Cox hazards analysis revealed that delayed ambulation was associated with long-term adverse events (hazard ratio 1.04 per day, P<0.001). With adjustment for preoperative factors, the estimated future risk of adverse events was found to be increased day-by-day during the delay until initial ambulation. Conclusions: In isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation protocol after cardiac surgery.

DOI： 10.1253/circj.CJ-22-0416

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestive Endoscopy  

Objectives: Comprehensive assessments of the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the elderly are unavailable. We aimed to create a scoring system to predict the long-term prognosis after ESD for EGC among patients aged ≥75 years. Methods: We conducted retrospective studies of two cohorts: a single-center cohort (2006–2011) for developing the scoring system, and a multicenter cohort for validating the developed system (2012–2016). In the development cohort, factors related to death after ESD were identified using multivariable Cox regression analysis, and a predictive scoring system was developed. In the validation cohort, the scoring system was validated in 295 patients. Results: In the development cohort, Charlson comorbidity index (CCI) ≥3 (hazard ratio [HR] 3.017), high psoas muscle index (PMI) (HR 2.206), and age ≥80 years (HR 1.978) were significantly related to overall survival after ESD. Therefore, high CCI, low PMI, and age ≥80 years were assigned 1 point each. The patients were categorized into low (≤1 point) and high (≥2 points) score groups based on their total scores. In the validation cohort, 184 and 111 patients were assigned to the low- and high-score groups, respectively. In comparisons based on Kaplan–Meier curves, the 5-year survival rate was 91.5% in the low-score group and 57.8% in the high-score group (log-rank test; P < 0.001). Conclusion: Our scoring system including high CCI, low PMI, and age ≥80 years could stratify the long-term prognosis of elderly patients aged ≥75 years after ESD for EGC.

DOI： 10.1111/den.14416

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestion  

Introduction: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. Methods: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. Results: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94-5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). Discussion/Conclusion: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients.

DOI： 10.1159/000528174

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PLoS ONE  

Achondroplasia (ACH) is a common skeletal dysplasia characterized by a disproportionately short stature. We found that meclizine, which is an over-the-counter drug for motion sickness, inhibited the fibroblast growth factor receptor 3 (FGFR3) gene using a drug repositioning strategy, and meclizine 1 and 2 mg/kg/day promoted bone growth in a mouse model of ACH. A previous phase 1a clinical trial for children with ACH demonstrated that a single dose of meclizine 25 and 50 mg was safe and that the simulated plasma concentration achieved steady state approximately 10 days after the first dose. The current study aimed to evaluate the safety and pharmacokinetics (PK) of meclizine in children with ACH after a 14-day-repeated dose of meclizine. Twelve patients with ACH aged 5–10 years were enrolled. Meclizine 12.5 (cohort 1) and 25 mg/day (cohort 2) were administered after meals for 14 days, and adverse events (AEs) and PK were evaluated. No patient experienced serious AEs in either group. The average (95% confidential interval [CI]) maximum drug concentration (Cmax), peak drug concentration (Tmax), area under the curve (AUC) from 0 to 24 h, and terminal elimination half-life (t1/2) after a 14-day-repeated administration of meclizine (12.5 mg) were 167 (83–250) ng/mL, 3.7 (3.1–4.2) h, 1170 (765–1570) ngh/mL, and 7.4 (6.7–8.0) h, respectively. The AUC0-6h after the final administration was 1.5 times that after the initial dose. Cmax and AUC were higher in cohort 2 than in cohort 1 in a dose-dependent manner. Regarding the regimen of meclizine 12.5 and 25 mg in patients < 20 kg and ≥ 20 kg, respectively, the average (95% CI) AUC0-24h was 1270 (1100–1440) ngh/mL. Compartment models demonstrated that the plasma concentration of meclizine achieved at a steady state after the 14th administration. Long-term administration of meclizine 12.5 or 25 mg/day is recommended for phase 2 clinical trials in children with ACH.

DOI： 10.1371/journal.pone.0283425

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Asia-Pacific Journal of Clinical Oncology  

Aims: The docetaxel and cisplatin plus 5-fluorouracil (5-FU) (DCF) regimen is expected to be superior to cisplatin plus 5-FU for the preoperative treatment of esophageal cancer. However, a high risk of adverse effects, including febrile neutropenia (FN), has been reported. To evaluate the effectiveness and safety of DCF with prophylactic pegfilgrastim, we conducted a phase II study. Methods: The regimen consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and a continuous infusion of 5-FU (750 mg/m2 per day) on days 1–5. A single 3.6-mg dose of pegfilgrastim was given as a subcutaneous injection on day 7 of each cycle. This regimen was repeated every 3 weeks for a maximum of three cycles. The primary endpoint was the grade-2/3 histopathological response rate. Results: Thirty-seven eligible patients were enrolled and received DCF. Thirty-four patients underwent esophagectomy. Two patients received chemoradiotherapy or radiotherapy without surgery. One patient withdrew consent and ended his hospital visit. One patient received additional radiotherapy before surgery. Histopathological responses of grade 3, grade 2, grade 1b, and grade 1a were observed in two (5.4%), 14 (37.8%), 10 (27.0%), and seven (18.9%) patients, respectively, and the primary endpoint was met. Of the 37 eligible patients, 11 (29.7%) developed FN in the first cycle. Conclusions: Since the histopathological responses were as expected, DCF with prophylactic pegfilgrastim is considered to be effective as preoperative chemotherapy. However, the prophylactic use of pegfilgrastim on day 7 was insufficient to prevent FN.

DOI： 10.1111/ajco.13755

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Journal of Emergency Medicine  

Objective: The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of the premorbid use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB) on short-term mortality in patients with sepsis. Data sources: Embase, the Cochrane Central Register of Controlled Trials, and MEDLINE were searched for studies based on the below eligibility criteria. The protocol was registered at the PROSPERO (CRD42022309129). Study selection: Eligibility criteria were as follows: (1) randomized controlled trials, cohort studies, cross-sectional studies, (2) patients with sepsis aged ≥16 years, and (3) received premorbid ACEI/ARB, or not. Data extraction: The patient and study characteristics and outcomes were extracted. All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as ≤30-day, in-hospital, or intensive care unit (ICU)- mortality. The secondary outcome was acute kidney injury (AKI). Data synthesis: Fifteen studies (N = 96,159) met the eligibility criteria. Of these, eleven studies (N = 40,360) reported unadjusted short-term mortalities. The pooled odds ratio (OR) of short-term mortality with the premorbid use of ACEI/ARB was as follows: OR, 0.86; 95% confidence interval (CI), 0.67 to 1.11; P = 0.24, I2 = 88%. Five studies reported an adjusted OR of short-term mortality with the premorbid use of ACEI/ARB as follows: OR, 0.74; 95%CI, 0.59 to 0.93; P < 0.01, I2 = 93%. Seven studies reported the pooled adjusted OR of AKI with the premorbid use of ACEI/ARB as follows: OR: 1.57, 95%CI: 1.26–1.96, p < 0.01, I2 = 69%. Conclusion: In this meta-analysis, the premorbid ACEI/ARB was associated with significantly lower short-term mortality in patients with sepsis despite the significantly higher risk of AKI.

DOI： 10.1016/j.ajem.2022.10.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Rheumatology (United Kingdom)  

DOI： 10.1093/rheumatology/keac170

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nagoya Journal of Medical Science  

It is difficult to identify patients with isolated dizziness caused by cerebrovascular events. The estimated risk of cerebrovascular events in isolated dizziness patients is not completely understood. We aimed to evaluate the association of the finger-to-nose test (FNT) in diagnosing cerebrovascular events in isolated dizziness patients in emergency departments (EDs). We combined 2 datasets from a single center for consecutive isolated dizziness patients, with the same inclusion and exclusion criteria. Those who met any of the following criteria were excluded: no FNT data, age < 16 years, and psychological trauma. The primary outcome was cerebrovascular event, which was defined as cerebral stroke due to cerebral infarction, cerebral hemorrhage, vertebral artery dissection, or transient ischemic attack. In the combined dataset, there were 357 patients complaining of isolated dizziness and 31 cerebrovascular events. After adjusted by 5 previously reported risk factors for cerebrovascular event, (age, hypertension, hyperlipidemia, diabetes mellitus, nystagmus), a multivariable logistic model analysis showed that the existence of FNT abnormalities was significantly associated with cerebrovascular events (odds ratio, 25.3; 95% confidence interval, 7.3–88.2; p < 0.001). There was a significant increase in predictive accuracy, with an AUC increase of 0.116 in the in a ROC analysis (p = 0.023). The existence of FNT abnormalities is considered as a strong risk factor that could be useful for predicting cerebrovascular events in isolated dizziness patients. We recommend the FNT for screening isolated dizziness patients in EDs to judge whether they need to undergo further diagnostic evaluation

DOI： 10.18999/nagjms.84.3.621

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Retained products of conception (RPOC) is a common cause of postpartum bleeding, which may be life-threatening; however, no evidence-based guidelines exist to assist in evaluating the risk of massive hemorrhage in women with RPOC. In this prospective study, we aimed to evaluate the predictive factors for massive hemorrhage in women with RPOC. The primary and secondary endpoints were to validate the usefulness of power Doppler color scoring (PDCS) in evaluating hypervascularity and to identify other predictive factors (such as maximum RPOC diameter and serum βhCG and Hb level at first visit), respectively. Among the 51 women with RPOC included in this study, 16 (31.5%) experienced massive hemorrhage during follow-up. None of the women with PDCS 1 or 2 (18) experienced massive hemorrhage, whereas 16 (48.5%) women with PDCS 3 or 4 (33) did. Multiple logistic regression analysis showed that the odds ratio [95% confidence interval] (P value) for PDCS, assisted reproductive technology (ART), and low serum hemoglobin (Hb) levels were 22.39 [2.25 − 3087.92] (P = 0.004), 5.72 [1.28 − 33.29] (P = 0.022), and 4.24 [0.97 − 22.99] (P = 0.056), respectively. Further, the decision tree method identified PDCS, ART, and low serum Hb levels as potential predictive factors for massive hemorrhage. This study identified PDCS as useful predictor of massive hemorrhage in women with RPOC. With additional inclusion of factors such as ART and low serum Hb levels, the risk of massive hemorrhage may be effectively evaluated, leading to better management of women of reproductive age.

DOI： 10.1038/s41598-022-15564-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of the American Heart Association  

BACKGROUND: Predicting a spontaneous rhythm change from non shockable to shockable before hospital arrival in patients with out-of-hospital cardiac arrest can help emergency medical services develop better strategies for prehospital treatment. The aim of this study was to identify predictors of spontaneous rhythm change before hospital arrival in patients with out-of-hospital cardiac arrest and develop a predictive scoring system. METHODS AND RESULTS: We retrospectively reviewed data of eligible patients with out-of-hospital cardiac arrest with an initial nonshockable rhythm registered in a nationwide registry between June 2014 and December 2017. We performed a multivari-able analysis using a Cox proportional hazards model to identify predictors of a spontaneous rhythm change, and a ridge regression model for predicting it. The data of 25 804 patients were analyzed (derivation cohort, n=17 743; validation cohort, n=8061). The rhythm change event rate was 4.1% (724/17 743) in the derivation cohort, and 4.0% (326/8061) in the validation cohorts. Age, sex, presence of a witness, initial rhythm, chest compression by a bystander, shock with an automated external defibrillator by a bystander, and cause of the cardiac arrest were all found to be independently associated with spontaneous rhythm change before hospital arrival. Based on this finding, we developed and validated the Rhythm Change Before Hospital Arrival for Nonshockable score. The Harrell’s concordance index values of the score were 0.71 and 0.67 in the internal and external validations, respectively. CONCLUSIONS: Seven factors were identified as predictors of a spontaneous rhythm change from nonshockable to shockable before hospital arrival. We developed and validated a score to predict rhythm change before hospital arrival.

DOI： 10.1161/JAHA.121.025048

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Life Science Alliance  

Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.

DOI： 10.26508/lsa.202101230

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Circulation Journal  

Background: Zinc (Zn) has been reported to play an important role in wound healing (WH). Nevertheless, the effect of Zn in chronic limb-threatening ischemia (CLTI) patients is unclear. This study investigated the effect of Zn on the clinical outcomes of CLTI patients undergoing bypass surgery. Methods and Results: This study reviewed 111 consecutive patients who underwent an infrainguinal bypass from 2012 to 2020. Patients with Zn deficiency (serum Zn level <60 μg/dL) received oral Zn supplementation and maintained a normal level until WH. This study aimed to explore: (1) the effect of Zn deficiency; and (2) Zn supplementation in Zn-deficient patients on the clinical outcomes of this cohort. Patients with Zn deficiency, Zn supplementation, and no Zn supplementation despite Zn deficiency accounted for 48, 21, and 42 patients, respectively. (1) Zn deficiency was associated with WH (HR, 0.47; 95% CI, 0.29-0.78: P=0.003), major adverse limb events (MALE) (HR, 2.53; 95% CI, 1.26-5.09: P=0.009), and major amputation or death (HR, 3.17; 95% CI, 1.51-6.63: P=0.002). (2) Zn supplementation was positively related to WH (HR, 2.30; 95% CI, 1.21-4.34: P=0.011). This result was confirmed using propensity score matching (HR, 2.24; 95% CI, 1.02-4.87: P=0.043). Conclusions: The current study revealed that Zn level was associated with clinical outcomes in CLTI patients after bypass surgery. Oral Zn supplementation could improve WH in these patients.

DOI： 10.1253/circj.CJ-21-0832

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestive Endoscopy  

Objectives: Endoscopic submucosal dissection (ESD) in the duodenum is challenging. The water pressure method (WP-ESD) has been developed with a decreased rate of perforation. However, details of perioperative adverse events of WP-ESD are unknown. The purpose of this study was to clarify the frequency and related factors of fecal incontinence and oral regurgitation during WP-ESD. Methods: A chart-based retrospective analysis was performed on 43 patients who underwent duodenal WP-ESD. The saline volume given into the body was calculated in all cases. All adverse events during WP-ESD until 6 weeks were extracted, and factors related to intraoperative fecal incontinence or oral regurgitation were analyzed. The frequency of fecal incontinence and oral regurgitation was also compared to those of 83 conventional ESD cases. Results: In WP-ESD, intraoperative fecal incontinence occurred in 12 (28%), oral regurgitation in six (14%), and aspiration pneumonia in one patient. For fecal incontinence, the infusion speed (saline volume divided by resection time) around 17 mL/min was a significant factor in multivariable analysis. For oral regurgitation, only tumor size was a significant factor in univariate analysis (P = 0.027). Significant difference was observed in the frequency of fecal incontinence between WP-ESD and conventional ESD (28% vs. 0%, P < 0.001), but no difference was observed in oral regurgitation or aspiration pneumonia. Conclusions: Intraoperative fecal incontinence is a unique adverse event of WP-ESD related to the infusion speed. WP-ESD did not pose a risk for oral regurgitation, but we should be aware of the risk in large tumor cases.

DOI： 10.1111/den.14070

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SICOT-J  

Introduction: Microsoft Kinect V2® (Kinect) is a peripheral device of Xbox® and acquires information such as depth, posture, and skeleton definition. In this study, we investigated whether Kinect can be used for human gait analysis. Methods: Ten healthy volunteers walked 20 trials, and each walk was recorded by a Kinect and infrared-and marker-based-motion capture system. Pearsona's correlation and overall agreement with a method of meta-Analysis of Pearsona's correlation coefficient were used to assess the reliability of each parameter, including gait velocity, gait cycle time, step length, hip and knee joint angle, ground contact time of foot, and max ankle velocity. Hip and knee angles in one gait cycle were calculated in Kinect and motion capture groups. Results: The coefficients of correlation for gait velocity (r = 0.92), step length (r = 0.81) were regarded as strong reliability. Gait cycle time (r = 0.65), minimum flexion angle of hip joint (r = 0.68) were regarded as moderate reliability. The maximum flexion angle of the hip joint (r = 0.43) and maximum flexion angle of the knee joint (r = 0.54) were regarded as fair reliability. Minimum flexion angle of knee joint (r = 0.23), ground contact time of foot (r = 0.23), and maximum ankle velocity (r = 0.22) were regarded as poor reliability. The method of meta-Analysis revealed that participants with small hip and knee flexion angles tended to have poor correlations in maximum flexion angle of hip and knee joints. Similar trajectories of hip and knee angles were observed in Kinect and motion capture groups. Conclusions: Our results strongly suggest that Kinect could be a reliable device for evaluating gait parameters, including gait velocity, gait cycle time, step length, minimum flexion angle of the hip joint, and maximum flexion angle of the knee joint.

DOI： 10.1051/sicotj/2022027

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Respiration  

Background: Several factors have been reported to affect the diagnostic yield of bronchoscopy with radial endobronchial ultrasound (R-EBUS) for peripheral pulmonary lesions (PPLs). However, it is difficult to accurately predict the diagnostic potential of bronchoscopy for each PPL in advance. Objectives: Our objective was to establish a predictive model to evaluate the diagnostic yield before the procedure. Method: We retrospectively analysed consecutive patients who underwent diagnostic bronchoscopy with R-EBUS between April 2012 and October 2015. We assessed the factors that were predictive of successful bronchoscopic diagnosis of PPLs with R-EBUS using a multivariable logistic regression model. The accuracy of the predictive model was evaluated using the receiver operator characteristic area under the curve (ROC AUC). Internal validation was analysed using 10-fold stratified cross-validation. Results: We analysed a total of 1,634 lesions; the median lesion size was 25.0 mm. Of these, 1,138 lesions (69.6%) were successfully diagnosed. In the predictive logistic model, significant factors affecting the diagnostic yield were lesion size, lesion structure, bronchus sign, and visible on chest X-ray. The predictive model consisted of seven factors: lesion size, lesion lobe, lesion location from the hilum, lesion structure, bronchus sign, visibility on chest X-ray, and background lung. The ROC AUC of the predictive model was 0.742 (95% confidence interval: 0.715-0.769). Internal validation using 10-fold stratified cross-validation revealed a mean ROC AUC of 0.734. Conclusions: The predictive model using the seven factors revealed a good performance in estimating the diagnostic yield.

DOI： 10.1159/000526574

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Neurology  

We evaluated the inner ear distribution of 17O-labeled saline administered to the human tympanic cavity. Magnetic resonance imaging was performed after intratympanic administration in five healthy volunteers and one patient with cochlear endolymphatic hydrops. In all volunteers, 17O-labeled water permeated the cochlear basal turn and vestibule at 30 min and disappeared gradually within 2–4 h. All participants experienced positional vertigo lasting a few hours to a few days. Visualization of 17O-labeled water distribution in the endolymphatic space of the posterior ampulla showed indistinct separation of endolymph and perilymph in the cochlea and most of the vestibule in all participants. Intralabyrinthine distribution of 17O-labeled water differed from that in previous reports of intratympanically administered gadolinium-based contrast agent. 17O-labeled water in the endolymphatic space may cause heavier endolymph and positional vertigo. These results of this study may add new insights for investigating the distribution and the effects of molecules in the inner ear after the intratympanic administration in living humans.

DOI： 10.3389/fneur.2022.1016577

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Critical Care Medicine  

OBJECTIVES: The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials to investigate whether IV high-dose vitamin C improves the short-term mortality of patients with sepsis. DESIGN: This study is a systematic review and meta-analysis of randomized controlled trials. We searched EMBASE, the Cochrane Central Register of Controlled Trials, and MEDLINE for randomized controlled trials that met inclusion criteria. The protocol was registered at the University hospital Medical Information Network Clinical Trials Registry (UMIN000040528). All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as 28-day, 30-day, or in-hospital mortality. PATIENTS: Two authors independently evaluated the following eligibility criteria: 1) randomized controlled trial, 2) patients with sepsis aged ≥18 years, and 3) received intravenous high-dose vitamin C in addition to standard of care, or standard of care alone. Then, two authors independently extracted the selected patient and study characteristics and outcomes from studies that met above eligibility criteria. MEASUREMENTS AND MAIN RESULTS: Eleven randomized controlled trials (n = 1,737 patients) were included in this meta-analysis. High-dose IV vitamin C was not associated with a significantly lower short-term mortality (risk ratio, 0.88; 95% CI, 0.73-1.06; p = 0.18; I2= 29%) but was associated with a significantly shorter duration of vasopressor use (standardized mean difference, -0.35; 95% CI, -0.63 to -0.07; p < 0.01; I2= 80%) and a significantly greater decline in the Sequential Organ Failure Assessment score at 72-96 hours (standardized mean difference, -0.20; 95% CI, -0.32 to -0.08; p < 0.01; I2= 16%). One study reported significant association with hypernatremia, but adverse effects were rare, and high-dose vitamin C is deemed relatively safe. CONCLUSIONS: In this meta-analysis, the use of IV high-dose vitamin C in patients with sepsis was not associated with lower short-term mortality although it was associated with significantly shorter duration of vasopressor use and greater decline in the Sequential Organ Failure Assessment score at 72-96 hours.

DOI： 10.1097/CCM.0000000000005263

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Journal of Emergency Medicine  

Study objective: Identification of pulmonary embolism (PE) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) carries significant therapeutic implications. We aimed to investigate the prevalence of PE in patients with AECOPD. Methods: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and Embase. We registered the protocol at the PROSPERO (CRD42021230481). Two authors independently evaluated whether titles and abstracts met the eligibility criteria, which were as follows: (1), prospective study or cross-sectional study in case the protocol for workup of PE was specified in advance, (2) patients with AECOPD aged ≥ 18 years, and (3) investigated the prevalence of PE or venous thromboembolism (VTE). Two authors independently extracted the selected patient and study characteristics and outcomes. We presented the results of all analyses with the use of random-effects models. The primary outcome was the prevalence of PE. Results: We included 16 studies (N = 4093 patients) in this meta-analysis. The prevalence of PE in patients with AECOPD was 12% [95% confidence interval (CI), 9 to 16%]. Substantial heterogeneity was observed (I2 = 94.8%). The pooled mortality was higher in patients with PE than those without (odds ratio 5.30, 95%CI: 2.48–11.30, p-value < 0.001). Conclusion: In this meta-analysis, the prevalence of PE in patients with AECOPD was 12% and the mortality of patients with PE was higher than those without. This suggests an acute necessity to develop validated diagnostic strategies for identifying PE in patients with AECOPD.

DOI： 10.1016/j.ajem.2021.09.041

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Intensive Care Medicine  

Objective: The aim of this study was to conduct a systematic review and meta-analysis to investigate the impact of premorbid beta-blockers on mortality in patients with sepsis. Data Sources: We searched EMBASE, the Cochrane Central Register of Controlled Trials, and MEDLINE for eligible studies. The protocol was registered at the PROSPERO (CRD42021256813). Study Selection: Two authors independently evaluated the following inclusion criteria: (1) randomized controlled trials, cohort studies, cross-sectional studies; (2) patients with sepsis aged ≥18 years, and (3) premorbid beta-blocker use. Data Extraction: Two authors extracted the patients’ characteristics and outcomes independently. All analyses were performed using the random-effects models. The primary outcome was short-term mortality, defined as mortality within 30 days, in-hospital or intensive care unit mortality. Data Synthesis: Ten studies (n = 24 748 patients) were included. The pooled odds ratio (OR) of short-term mortality associated with the premorbid use of beta-blockers was 0.85 (95% confidence interval [CI], 0.69-1.04; P =.12; I2 = 50%). Five studies reported an adjusted OR of short-term mortality. The pooled adjusted OR of short-term mortality associated with the premorbid use of beta-blockers was 0.73 (95% CI, 0.65-0.83; P <.001; I2 = 0%). Conclusion: Premorbid beta-blockers were associated with a lower short-term mortality in patients with sepsis.

DOI： 10.1177/08850666211052926

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Resuscitation  

Introduction: The objective of this cohort study was to investigate whether the revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia score (rCAST), which we previously developed as a prognostic score for adult patients with post-cardiac arrest syndrome (PCAS), is also applicable to pediatric patients. Methods: Pediatric PCAS patients were included from an out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM). We validated the predictive accuracy of the rCAST for the neurological outcomes at 30 and 90 days. We also evaluated the probability of a good neurological outcome in each of the three specified severity categories based on the rCAST (low severity: ≤5.5; moderate severity: 6.0–14.0; high severity: ≥14.5). Results: Among the 737 pediatric patients with OHCA, the data of 179 pediatric PCAS patients in whom return of spontaneous circulation was achieved were analyzed. The areas under the curve (AUC) of the rCAST for predicting the neurological outcomes at 30 days and 90 days were 0.95 (95% CI: 0.90–0.99) and 0.96 (0.91–1.00), respectively. The proportions of patients with a good neurological outcome at 30 days were 100% (12/12) in the low severity group, 36.1% (13/36) in the moderate severity group, and 2.3% (3/131) in the high severity group. Conclusions: The AUC of the rCAST for pediatric PCAS patients was found to be greater than 0.9 in the external validation, which corresponds to excellent predictive accuracy. There was no patient with good neurological outcome among the patients with more than 17.0 points (extremely high severity group).

DOI： 10.1016/j.resuscitation.2021.09.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：General Thoracic and Cardiovascular Surgery  

Objective: Aortic surgery often causes massive bleeding due to hypofibrinogenemia. Predicting hypofibrinogenemia is useful for developing a hemostasis strategy, including preparing for blood transfusion. We made a formula for predicting the serum fibrinogen level (SFL) at the termination of cardiopulmonary bypass (CPB) in aortic surgery and examined its validity. Methods: We performed a retrospective observational study that consisted of 267 patients (group A) who underwent aortic surgery from July 2013 to December 2016 and made a formula for predicting the SFL at the termination of CPB in group A by a multiple linear regression analysis. The validity of this formula was then examined in another 60 patients (group B) who underwent aortic surgery from January 2017 to December 2017. Results: We developed the following predictive formula: SFL at the termination of CPB (mg/dL) = 14.7 + 0.44 × preoperative SFL (mg/dL) + (− 0.14) × CPB time (min) + 0.64 × preoperative body weight (kg) + (− 17.3) × lateral thoracotomy (Yes/No, Yes: 1, No: 0). In group B, the predictive formula proved to be statistically valid in group B (R2 = 0.531, p < 0.001). Conclusion: The SFL at the termination of CPB in aortic surgery can be predicted by the preoperative SFL, body weight, CPB time and surgical approach. The predictive formula is useful for developing a hemostasis strategy, including preparing for blood transfusion.

DOI： 10.1007/s11748-021-01594-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

We retrospectively analyzed data from the Medical Information Mart for Intensive Care-III critical care database to determine whether visually-assessed right ventricular (RV) dysfunction was associated with clinical outcomes in septic shock patients. Associations between visually-assessed RV dysfunction by echocardiography and in-hospital mortality, lethal arrhythmia, and hemodynamic indicators to determine the prognostic value of RV dysfunction in patients with septic shock were analyzed. Propensity score analysis showed RV dysfunction was associated with increased risk of in-hospital death in patients with septic shock (adjusted odds ratio [OR] 2.15; 95% confidence interval [CI] 1.99–2.32; P < 0.001). In multivariate logistic regression analysis, RV dysfunction was associated with in-hospital death (OR 2.19; 95% CI 1.91–2.53; P < 0.001), lethal arrhythmia (OR 2.19; 95% CI 1.34–3.57; P < 0.001), and tendency for increased blood lactate levels (OR 1.31; 95% CI 1.14–1.50; P < 0.001) independent of left ventricular (LV) dysfunction. RV dysfunction was associated with lower cardiac output, pulmonary artery pressure index, and RV stroke work index. In patients with septic shock, visually-assessed RV dysfunction was associated with in-hospital mortality, lethal arrhythmia, and circulatory insufficiency independent of LV dysfunction. Visual assessment of RV dysfunction using echocardiography might help to identify the short-term prognosis of patients with septic shock by reflecting hemodynamic status.

DOI： 10.1038/s41598-021-98397-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Critical Care Medicine  

OBJECTIVES: The optimal target temperature during targeted temperature management for patients after cardiac arrest remains under debate. The aim of this study was to evaluate the association between targeted temperature management at lower target temperatures and the neurologic outcomes among patients classified by the severity of postcardiac arrest syndrome. DESIGN: A multicenter observational study from the out-of-hospital cardiac arrest registry of the Japanese Association for Acute Medicine, which is a nationwide prospective registry of out-of-hospital cardiac arrest patients. SETTING: A total of 125 critical care medical centers or hospitals with an emergency care department across Japan. PATIENTS: A total of 1,111 out-of-hospital cardiac arrest patients who had received targeted temperature management. MEASUREMENTS AND MAIN RESULTS: We divided all 1,111 postcardiac arrest syndrome patients treated with targeted temperature management into two groups: those who received targeted temperature management at a lower target temperature (33-34°C) and those who received targeted temperature management at a higher target temperature (35-36°C). In regard to classification of the patients, we divided the patients into three categories of severity (low, moderate, and high severities) using the risk classification tool, post-Cardiac Arrest Syndrome for Therapeutic hypothermia, which was previously validated. The primary outcome was the percentage of patients with a good neurologic outcome at 30 days, and the secondary outcome was the survival rate at 30 days. Multivariate analysis showed that targeted temperature management at 33-34°C was significantly associated with a good neurologic outcome and survival at 30 days in the moderate severity (odds ratio, 1.70 [95% CI, 1.03-2.83] and 1.90 [95% CI, 1.15-3.16], respectively), but not in the patients of low or high severity (pinteraction= 0.033). Propensity score analysis also showed that targeted temperature management at 33-34°C was associated with a good neurologic outcome in the moderate-severity group (p = 0.022). CONCLUSIONS: Targeted temperature management at 33-34°C was associated with a significantly higher rate of a good neurologic outcome in the moderate-severity postcardiac arrest syndrome group, but not in the low- or high-severity group.

DOI： 10.1097/CCM.0000000000005025

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

In sepsis-associated coagulopathies and disseminated intravascular coagulation, relative platelet reductions may reflect coagulopathy severity. However, limited evidence supports their clinical significance and most sepsis-associated coagulopathy criteria focus on the absolute platelet counts. To estimate the impact of relative platelet reductions and absolute platelet counts on sepsis outcomes. A multicenter retrospective observational study was performed using the eICU Collaborative Research Database, comprising 335 intensive care units (ICUs) in the United States. Patients with sepsis and an ICU stay > 2 days were included. Estimated effects of relative platelet reductions and absolute platelet counts on mortality and coagulopathy-related complications were evaluated. Overall, 26,176 patients were included. Multivariate mixed-effect logistic regression analysis revealed marked in-hospital mortality risk with larger platelet reductions between days one and two, independent from the resultant absolute platelet counts. The adjusted odds ratio (OR) [95% confidence intervals (CI)] for in-hospital mortality was 1.28[1.23–1.32], 1.86[1.75–1.97], 2.99[2.66–3.36], and 6.05[4.40–8.31] for 20–40%, 40–60%, 60–80%, and > 80% reductions, respectively, when compared with a < 20% decrease in platelets (P < 0.001 for each). In the multivariate logistic regression analysis, platelet reductions ≥ 11% and platelet counts ≤ 100,000/μL on day 2 were associated with high coagulopathy-related complications (OR [95%CI], 2.03 and 1.18; P < 0.001 and P < 0.001), while only platelet reduction was associated with thromboembolic complications (OR [95%CI], 1.43 [1.03–1.98], P < 0.001). The magnitude of platelet reductions represent mortality risk and provides a better signature of coagulopathies in sepsis; therefore, it is a plausible criterion for sepsis-associated coagulopathies.

DOI： 10.1038/s41598-021-93635-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Clinical Medicine  

Whether a patient with severe coronavirus disease (COVID-19) will be successfully liberated from mechanical ventilation (MV) early is important in the COVID-19 pandemic. This study aimed to characterize the time course of parameters and outcomes of severe COVID-19 in relation to the timing of liberation from MV. This retrospective, single-center, observational study was performed using data from mechanically ventilated COVID-19 patients admitted to the ICU between 1 March 2020 and 15 December 2020. Early liberation from ventilation (EL group) was defined as successful extubation within 10 days of MV. The trends of respiratory mechanics and laboratory data were visualized and compared between the EL and prolonged MV (PMV) groups using smoothing spline and linear mixed effect models. Of 52 admitted patients, 31 mechanically ventilated COVID-19 patients were included (EL group, 20 (69%); PMV group, 11 (31%)). The patients’ median age was 71 years. While in-hospital mortality was low (6%), activities of daily living (ADL) at the time of hospital discharge were significantly impaired in the PMV group compared to the EL group (mean Barthel index (range): 30 (7.5–95) versus 2.5 (0–22.5), p = 0.048). The trends in respiratory compliance were different between patients in the EL and PMV groups. An increasing trend in the ventilatory ratio during MV until approximately 2 weeks was observed in both groups. The interaction between daily change and earlier liberation was significant in the trajectory of the thrombin–antithrombin complex, antithrombin 3, fibrinogen, C-reactive protein, lymphocyte, and positive end-expiratory pressure (PEEP) values. The indicator of physiological dead space increases during MV. The trajectory of markers of the hypercoagulation status, inflammation, and PEEP were significantly different depending on the timing of liberation from MV. These findings may provide insight into the pathophysiology of COVID-19 during treatment in the critical care setting.

DOI： 10.3390/jcm10112513

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Critical Care  

Purpose: The predictive value of airway occlusion pressure at 100 milliseconds (P0.1) on weaning outcome has been controversial. We performed a meta-analysis to investigate the predictive value of P0.1 on successful weaning from mechanical ventilation. Materials and methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE, and two authors independently screened articles. The pooled sensitivity, specificity and the summary receiver operating characteristic (sROC) curve were estimated. Diagnostic odds ratio (DOR) was calculated using meta-regression analysis. Results: We included 12 prospective observational studies (n = 1089 patients). Analyses of sROC curves showed the area under the curve of 0.81 (95% confidence interval (CI): 0.77 to 0.84) for P0.1. The pooled sensitivity and specificity were 86% (95% CI, 72 to 94%) and 58% (95% CI, 37% to 76%) with substantial heterogeneity respectively. DOR was 20.09 (p = 0.019, 95%CI: 1.63–247.15). After filling the missing data using the trim-and-fill method to adjust publication bias, DOR was 36.23 (p = 0.002, 95%CI: 3.56–372.41). Conclusion: This meta-analysis suggests that P0.1 is a useful tool to predict successful weaning. To determine clinical utility, a large prospective study investigating the sensitivity and specificity of P0.1 on weaning outcomes from mechanical ventilation is warranted.

DOI： 10.1016/j.jcrc.2020.09.030

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Chest  

Background: Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation. Research Question: Do ultrashort-acting β-blockers such as esmolol and landiolol improve mortality in patients with sepsis with persistent tachycardia despite initial resuscitation? Study Design and Methods: This was a systematic review and meta-analysis. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with esmolol or landiolol. We updated our search on April 20, 2020. Two independent reviewers assessed whether titles and abstracts met the following eligibility criteria: (1) RCT, (2) patients with sepsis and septic shock ≥ 18 years of age, and (3) treatment with either esmolol/landiolol or placebo/no interventions. Two authors independently extracted selected patient and study characteristics and outcomes. The results of all analyses are presented using random effect models. Results: Seven RCTs with a pooled sample size of 613 patients were included. Of these, six RCTs with 572 patients reported 28-day mortality. Esmolol or landiolol use in patients with sepsis and septic shock was significantly associated with lower 28-day mortality (risk ratio, 0.68; 95% CI, 0.54-0.85; P <.001). Unimportant heterogeneity was observed (I2 = 31%). The absolute risk reduction and number of patients to be treated to prevent one death were 18.2% and 5.5, respectively. Interpretation: The use of ultrashort-acting β-blockers such as esmolol and landiolol in patients with sepsis with persistent tachycardia despite initial resuscitation was associated with significantly lower 28-day mortality. Trial Registry: UMIN Clinical Trials Registry; No.: UMIN000040174; URL: https://www.umin.ac.jp/ctr/index.htm;

DOI： 10.1016/j.chest.2021.01.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PLoS ONE  

A previous study has shown that late failure (> 48 hours) of high-flow nasal cannula (HFNC) was associated with intensive care unit (ICU) mortality. The aim of this study was to investigate whether failure of non-invasive respiratory support, including HFNC and non-invasive positive pressure ventilation (NPPV), was also associated with the risk of mortality even if it occurs in the earlier phase. We retrospectively analyzed 59 intubated patients for acute respiratory failure due to lung diseases between April 2014 and June 2018. We divided the patients into 2 groups according to the time from starting non-invasive ventilatory support until their intubation: ≤6 hours failure and > 6 hours failure group. We evaluated the differences in the ICU mortality between these two groups. The multivariate logistic regression analysis showed the highest mortality in the > 6 hours failure group as compared to the ≤6 hours failure group, with a statistically significant difference (p < 0.01). It was also associated with a statistically significant increased 30-day mortality and decreased ventilator weaning rate. The ICU mortality in patients with acute respiratory failure caused by lung diseases was increased if the time until failure of HFNC and NPPV was more than 6 hours.

DOI： 10.1371/journal.pone.0251030

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Digestion  

Introduction: Endoscopic criteria for the diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs) are lacking. The aim of this study was to explore the usefulness of endocytoscopy (ECS) in the duodenum. Methods: A total of 77 ECS images stained by methylene blue and 58 images with double staining of methylene blue and crystal violet were obtained from 20 patients. Images were classified into 3 grades based on nuclear and villi atypia: EC A, B, and C. Diagnostic performance of ECS classification to predict histology and interobserver agreement was evaluated. The performance was compared between staining methods and ×520 or ×936 zoom. Results: With methylene blue staining, high rates of accuracy, sensitivity, specificity, and positive predictive value (PPV) over 90% were achieved for tumor and nontumor diagnosis as assessed by EC A versus EC B. High rates of accuracy, sensitivity, PPV, and negative predictive value over 90% were achieved for the differentiation between the diagnosis of the Vienna category 3 and 4/5 as assessed by EC B versus C. The accuracy rate of interpreting ECS images with ×936 zoom among 10 endoscopists was 82%, and the interobserver agreement rate was 0.803 (Kendall's coefficient of concordance). In the ×936 zoom group, methylene blue staining was significantly associated with higher accuracy rate (odds ratio 1.76 [1.06-2.92], p value 0.0297). No benefit was observed by double staining. Conclusions: ECS diagnosis with methylene blue provides a high accuracy rate and good interobserver agreement to predict histology of SNADETs.

DOI： 10.1159/000516512

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SICOT-J  

Introduction: Trochanteric femoral fracture is one of the most common fractures in the elderly. Trochanteric femoral fracture with involvement of the lesser trochanter is considered unstable and recognized as having a poor prognosis. However, fixation of lesser trochanter fragment is scarce because of technical difficulties. In this study, we reported the simple surgical procedure and the effect of using nonabsorbable tape in lesser trochanter fixation. Methods: From January 2014 to December 2017, 114 patients treated with proximal intramedullary nailing for trochanteric fractures with the lesser trochanter fragment were reviewed. Among patients enrolled in this study, 73 were followed up until radiographic bone union, of which 26 were treated with lesser trochanter fragment banding (group B) and 47 without banding (group N). Radiographs and/or computed tomography images were used to evaluate bone union of the lesser trochanter fragment at three months postoperatively. Results: The bone union of the lesser trochanter fragment was achieved in 24 cases (92%) in group B and 30 cases (64%) in group N. Compared with group N, group B showed a significantly increased number of mild and moderate deformities but decreased number of severe deformity and nonunion (P < 0.001). Postoperative complications were not observed in both groups. Conclusions: From the viewpoint of increasing lesser trochanteric bone union ratio, fixation of the lesser trochanter fragment using nonabsorbable tape in the treatment of trochanteric fractures could be an effective procedure.

DOI： 10.1051/sicotj/2021032

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Diagnostics  

ABO blood groups have been implicated as potential risk factors for various diseases. However, no study has investigated the association between sepsis mortality and ABO blood types. We aimed to evaluate the impact of these blood types on mortality in patients with sepsis and septic shock. This retrospective observational study was conducted at two general hospitals in Japan. Patients diagnosed with sepsis or septic shock were included and divided into four groups based on blood type (O, A, B, and AB). The association between type O vs. other types and 28- and 90-day mortalities was evaluated using multivariate logistic regression analysis adjusted for age, sex, and Sequential (Sepsis-related) Organ Failure Assessment score. This study included 415 patients, of whom 131 (31.6%), 171 (41.2%), 81 (19.5%), and 32 (7.7%) had type O, A, B, and AB, respectively. Blood type O was not associated with 28-day (odds ratio: 1.7 p = 0.08) or 90-day mortality (odds ratio: 1.53, p = 0.091). However, type O was significantly associated with higher 90-day mortality (odds ratio: 3.26, p = 0.009) in patients with septic shock. The role of ABO blood type in risk stratification for septic shock and the mechanisms that potentially affect the prognosis of sepsis patients need further investigation.

DOI： 10.3390/diagnostics10100826

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Clinical Medicine  

Sepsis-induced coagulopathy has poor prognosis; however, there is no established tool for predicting it. We aimed to create predictive models for coagulopathy progression using machine-learning techniques to evaluate predictive accuracies of machine-learning and conventional techniques. A post-hoc subgroup analysis was conducted based on the Japan Septic Disseminated Intravascular Coagulation retrospective study. We used the International Society on Thrombosis and Haemostasis disseminated intravascular coagulation (DIC) score to calculate the ∆DIC score as ((DIC score on Day 3) − (DIC score on Day 1)). The primary outcome was to determine whether the predictive accuracy of ∆DIC was more than 0. The secondary outcome was the actual predictive accuracy of ∆DIC (predicted ∆DIC−real ∆DIC). We used the machine-learning methods, such as random forests (RF), support vector machines (SVM), and neural networks (NN); their predictive accuracies were compared with those of conventional methods. In total, 1017 patients were included. Regarding DIC progression, predictive accuracy of the multiple linear regression, RF, SVM, and NN models was 63.7%, 67.0%, 64.4%, and 59.8%, respectively. The difference between predicted ∆DIC and real ∆DIC was 2.05, 1.54, 2.24, and 1.77 for the multiple linear regression, RF, SVM, and NN models, respectively. RF had the highest predictive accuracy.

DOI： 10.3390/jcm9072113

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nagoya Journal of Medical Science  

High-flow nasal cannula (HFNC) oxygen is a therapy that has demonstrated survival benefits in acute respiratory failure (ARF). However, the role of HFNC in ARF due to interstitial pneumonia (IP) is unknown. The aim of this study was to compare the effects of HFNC therapy and non-invasive positive pressure ventilation (NPPV) in ARF due to IP. This retrospective observational study included 32 patients with ARF due to IP who were treated with HFNC (n = 13) or NPPV (n = 19). The clinical characteristics, intubation rate and 30-day mortality were analyzed and compared between the HFNC group and the NPPV group. Predictors of 30-day mortality were evaluated using a logistic regression model. HFNC group showed higher mean arterial blood pressure (median 92 mmHg; HFNC group vs 74 mmHg; NPPV group) and lower APACHEII score (median 22; HFNC group vs 27; NPPV group) than NPPV group. There was no significant difference in the intubation rate at day 30 between the HFNC group and the NPPV group (8% vs 37%: p = 0.069); the mortality rate at 30 days was 23% and 63%, respectively. HFNC therapy was a significant determinant of 30-day mortality in univariate analysis, and was confirmed to be an independent significant determinant of 30-day mortality in multivariate analysis (odds ratio, 0.148; 95% confidence interval, 0.025-0.880; p = 0.036). Our findings suggest that HFNC therapy can be a possible option for respiratory management in ARF due to IP. The results observed here warrant further investigation of HFNC therapy in randomized control trials.

DOI： 10.18999/nagjms.82.2.301

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Critical Care Explorations  

Objectives: Abnormal secretion of catecholamines is well known to cause delirium. In particular, disturbances of catecholamine balance can cause ICU-acquired delirium. The aim of this study was to evaluate the association between the serum levels of catecholamines and the risk of occurrence of ICU-acquired delirium separately in patients who had/had not received exogenous catecholamines before ICU admission. Design: A secondary analysis of the data of 81 patients enrolled in our previous randomized clinical trial. Setting: ICU of an academic hospital. Patients: ICU patients in whom the serum levels of catecholamines were measured at ICU admission. Interventions: None. Measurements and Main Results: We evaluated the association between the serum levels of catecholamines measured at ICU admission and the risk of ICU-acquired delirium separately in patients who had received exogenous catecholamines at ICU admission (Ex[+] group) and those who had not received exogenous catecholamines (Ex[-] group). The serum levels of norepinephrine measured at ICU admission were significantly associated with the risk of ICU-acquired delirium in the Ex(-) group (odds ratio, 2.58; 95% CI, 1.02-6.52; p = 0.046), but not in the Ex(+) group (odds ratio, 1.02; 95% CI, 0.88-1.18; p = 0.823). Furthermore, there was a statistically significant interaction effect between the serum levels of norepinephrine and the use/nonuse of exogenous catecholamines at ICU admission in relation to the risk of occurrence of ICU-acquired delirium (pinteraction = 0.017). Conclusions: The serum levels of norepinephrine measured at admission were associated with the risk of occurrence of ICU-acquired delirium in patients who had not received exogenous catecholamines at ICU admission, whereas no such association was observed in those who had received exogenous catecholamines previously. Thus, the association between the serum levels of catecholamines measured at admission and the risk of ICU-acquired delirium differed between patients who had/had not received exogenous catecholamines at ICU admission.

DOI： 10.1097/CCE.0000000000000082

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ams2.561

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Intensive Care Medicine  

Background: The management of refractory septic shock remains a major challenge in critical care and its early indicators are not fully understood. We hypothesized that the maximum norepinephrine dosage within 24 hours of intensive care unit (ICU) admission may be a useful indicator of early mortality in patients with septic shock. Methods: In this retrospective single-center observational study, patients with septic shock admitted to the emergency ICU of an academic medical center between April 2011 and March 2017 were included. Individuals with cardiac arrest and those with do-not-resuscitate orders before admission were excluded. We analyzed if the maximum norepinephrine dosage within 24 hours of ICU admission (MD24) was associated with 7-day mortality. Results: Among 152 patients with septic shock, 20 (15%) did not survive by day 7. The receiver operating characteristic curve analysis for predicting 7-day mortality revealed a cutoff of MD24 of 0.6 μg/kg/min (sensitivity 47%, specificity 93%). In the multivariable regression analysis, a higher MD24 was significantly associated with 7-day mortality (odds ratio: 7.20; 95% confidence interval [CI]: 2.02-25.7; P =.002) but not with 30-day mortality. Using the inverse probability of treatment weighting method in a propensity scoring analysis, a higher MD24 was significantly associated with 7-day (hazard ratio [HR]: 8.9; 95% CI: 3.2-25.0; P <.001) and 30-day mortality (HR: 2.7; 95% CI: 1.2-5.8; P =.012). Conclusions: An MD24 ≥0.6 μg/kg/min was significantly associated with 7-day mortality in patients with septic shock and may therefore be a useful indicator of refractory septic shock.

DOI： 10.1177/0885066619860736

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Critical Care Explorations  

Objectives: To clarify the relationship between mobility disability at the time of discharge from the ICU and clinical factors evaluated at ICU admission in septic patients. Design: A single-center, retrospective, observational study. Setting: Ten-bed, the emergency and medical ICU. Patients: We analyzed the data of septic patients who were admitted to our ICU between September 2012 and September 2016 and received early rehabilitation. Interventions: None. Measurements and Main Results: The patients were categorized into two groups based on their scores on the ICU mobility scale at the time of discharge from the ICU: The mobility disability group (ICU mobility scale score < 9) and the no mobility disability group (ICU mobility scale score ≥ 9). Of the 110 eligible patients, 63 met the inclusion criteria; of these, 46 patients (73%) were classified into the mobility disability group, and 17 patients (27%) were classified into the no mobility disability group. The age (median, 72 vs 64 yr; p = 0.024), prevalence of patients with clinical frailty scale scores of greater than or equal to 5 (54% vs 12%; p = 0.003), Sequential Organ Failure Assessment score (median, 9.0 vs 6.0; p = 0.006) and rate of vasopressin use (26% vs 0%; p = 0.026) were significantly higher in the mobility disability group as compared with the no mobility disability group. Among the candidate variables for which values recorded before/at the time of ICU admission were available, the clinical frailty scale score was identified as the only independent, statistically significant predictor of mobility disability at ICU discharge (odds ratio, 7.77; 95% CI, 1.37-44.21; p = 0.021). The positive predictive value and negative predictive value of clinical frailty scale scores greater than or equal to 5 for mobility disability at ICU discharge were 92.6% and 41.7%, respectively. Conclusions: The clinical frailty scale score was associated with increased mobility disability at ICU discharge in septic patients receiving early rehabilitation.

DOI： 10.1097/CCE.0000000000000066

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Clinical Oncology  

Background: Treatment modality of desmoid-type fibromatosis (DF) has changed from surgery with a wide surgical margin to conservative treatment. In this study, tumor characteristics of DF, transition of the treatment modality, and clinical outcome of surgical treatment were analyzed based on data obtained from the bone and soft tissue tumor registry established in Japan. Methods: Data were collected as registration data and follow-up data. Five hundred and thirty registered cases of DF were identified, including 223 cases with follow-up data with or without surgical treatment. Results: The number of registered patients increased gradually. The frequency of surgical treatment was gradually reduced year by year. The 3-year local recurrence free survival (LRFS) was 77.7%, with tumor location and size tending to correlate with LRFS. Interestingly, there was no significant difference in LRFS between wide and marginal margin (P = 0.34). Conclusions: The treatment modality has shifted from surgical to conservative treatment, with risk factors for surgical treatment similar to those noted in previous studies. The National registry system is crucial for a rare disease such as DF, and in the future, a population based registry system should be established to better comprehend the actual status of DF.

DOI： 10.1007/s10147-019-01512-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Investigative Ophthalmology and Visual Science  

PURPOSE. A posterior staphyloma has been reported to be present in some eyes with retinitis pigmentosa (RP), and the purpose of this study was to determine the macular curvature of non-highly myopic RP eyes. METHODS. This was a retrospective, observational study. The medical charts of the right eyes of 143 patients with RP and 60 controls whose axial length ranged from 21.5 mm to 26.0 mm were reviewed. The mean curvature of Bruch’s membrane within 6 mm of the central macula obtained from the horizontal optical coherence tomographic images were evaluated as the mean macular curvature index (MMCI). The relationships between the MMCI and other clinical factors were assessed. RESULTS. The mean MMCI of RP patients (13.73 6 9.63 3 10−5 lm−1) was significantly lower than that of the controls (−6.63 6 5.63 3 10−5 lm−1). This indicated a deeper concave shape of the macula in RP eyes (P < 0.001). The MMCI was significantly correlated with the age (r = 0.20; P=0.016) and the axial length (r −0.24; P 0.004). Further analysis suggested a nonlinear effect of the ellipsoid zone width on the macular curvature in the RP eyes. CONCLUSIONS. There is a high incidence of steeper macular curvatures even in non-highly myopic RP eyes, and the steepness was also affected by the degree of photoreceptor degeneration.

DOI： 10.1167/iovs.19-27334

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Resuscitation  

Introduction: There are no established risk classification for post-cardiac arrest syndrome (PCAS) patients at the Emergency Department (ED) undergoing targeted temperature management (TTM). The aim of this study was to externally validate a simplified version of our prognostic score, the “post-Cardiac Arrest Syndrome for Therapeutic hypothermia score” (revised CAST [rCAST]) and estimate the predictive accuracy of the risk classification based on it. Methods: For the external validation, we used data from an out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM), which is a multicenter, prospective registry of OHCA patients across Japan. Eligible patients were PCAS patients treated with TTM at 33–36 °C between June 2014 and December 2015. We validated the accuracy of rCAST for predicting the neurological outcomes at 30 and 90 days. Results: Among the 12,024 OHCA patients, the data of 460 PCAS patients treated by TTM were eligible for the validation. The areas under the curve of rCAST for predicting the neurological outcomes at 30 and 90 days were 0.892 and 0.895, respectively. The estimated sensitivity and specificity of the risk categories for the outcomes were as follows: 0.95 (95% CI: 0.92–0.98) and 0.47 (0.40–0.55) for the low (rCAST: ≤5.5), 0.62 (0.56–0.68) and 0.48 (0.40–0.55) for the moderate (rCAST: 6.0–14.0), and 0.57 (0.51–0.63) and 0.95 (0.91–0.98) for the high severity category (rCAST: ≥14.5). Conclusions: The rCAST was useful for predicting the neurological outcomes with high accuracy in PCAS patients, and the three grades was developed for a risk classification based on the rCAST.

DOI： 10.1016/j.resuscitation.2019.05.028

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Intensive Care  

Background: We examined whether high lactate level in septic patients was associated with 90-day mortality based on the patients' disseminated intravascular coagulation (DIC) status. Methods: We conducted a multicenter, retrospective, observational study of patients admitted to the intensive care unit (ICU) with a suspicion of severe infection and diagnosed with sepsis. Regression analyses were performed to estimate the interaction effect between DIC status and the lactate level. Then, the association between the lactate level and 90-day mortality was assessed in the DIC and non-DIC subgroups. Results: The data of 415 patients were analyzed. We found a significant interaction between DIC status and the lactate level for predicting 90-day mortality (p interaction = 0.04). Therefore, we performed a subgroup analysis and found that high lactate concentration was significantly associated with 90-day mortality in the DIC group (odds ratio = 2.31, p = 0.039) but not in the non-DIC group. Conclusions: In patients with DIC, a high lactate level significantly predicted 90-day mortality; no such association was found in the non-DIC group. Thus, DIC status may serve as a possible effect modifier of lactate level in predicting mortality in patients with sepsis.

DOI： 10.1186/s40560-019-0389-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Intensive Care  

Background: Currently, the appropriate method of management of patients with refractory septic shock remains unclear. This study aimed to evaluate the factors associated with response to epinephrine in norepinephrine-refractory septic shock. Methods: A retrospective single-center observational study was performed using data from adult patients (≥ 18 years old) admitted to our emergency and medical intensive care unit (ICU) from January 2014 to December 2017 who had received epinephrine to treat norepinephrine-refractory septic shock. The response was considered positive if there was increase in mean arterial pressure of 10 mmHg or decrease in arterial lactate level 3 h after epinephrine administration. Results: Forty-one patients were included: 24 responders (59%) and 17 non-responders (41%). Responders showed higher rate of survival from shock (92% vs. 18%; P < 0.001), and 28-day survival (83% vs. 18%; P < 0.001). In multivariable analysis, time of epinephrine administration after ICU admission (odds ratio [OR] 0.48; 95% confidence interval [CI] 0.27-0.87; P = 0.011) and SOFA score (OR 0.19; 95% CI 0.04-0.88; P = 0.034) were associated with epinephrine response. Time of epinephrine administration was also significantly associated with survival from shock (OR 0.42; P = 0.005) and 28-day survival (OR 0.14; P = 0.006), while SOFA score did not. Using inverse probability of treatment weighing (IPTW) adjustment of propensity score, epinephrine administration later than 24 h after ICU admission was associated with poor response (OR 0.07; 95% CI 0.02-0.21; P < 0.001). Conclusions: Early administration of epinephrine after ICU admission (i.e., within 24 h) is associated with better hemodynamic status in patients with refractory septic shock.

DOI： 10.1186/s40560-019-0377-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Free Radical Research  

Exposure to asbestos fiber is central to mesothelial carcinogenesis, for which iron overload in or near mesothelial cells is a key pathogenic mechanism. Alternatively, iron chelation therapy with deferasirox or regular phlebotomy was significantly preventive against crocidolite-induced mesothelial carcinogenesis in rats. However, the role of iron transporters during asbestos-induced carcinogenesis remains elusive. Here, we studied the role of divalent metal transporter 1 (DMT1; Slc11a2), which is a Fe(II) transporter, that is present not only on the apical plasma membrane of duodenal cells but also on the lysosomal membrane of every cell, in crocidolite-induced mesothelial carcinogenesis using DMT1 transgenic (DMT1Tg) mice. DMT1Tg mice show mucosal block of iron absorption without cancer susceptibility under normal diet. We unexpectedly found that superoxide production was significantly decreased upon stimulation with crocidolite both in neutrophils and macrophages of DMT1Tg mice, and the macrophage surface revealed higher iron content 1 h after contact with crocidolite. Intraperitoneal injection of 3 mg crocidolite ultimately induced malignant mesothelioma in ∼50% of both wild-type and DMT1Tg mice (23/47 and 14/28, respectively); this effect was marginally (p = 0.069) delayed in DMT1Tg mice, promoting survival. The promotional effect of nitrilotriacetic acid was limited, and the liver showed significantly higher iron content both in DMT1Tg mice and after crocidolite exposure. The results indicate that global DMT1 overexpression causes decreased superoxide generation upon stimulation in inflammatory cells, which presumably delayed the promotional stage of crocidolite-induced mesothelial carcinogenesis. DMT1Tg mice with low-stamina inflammatory cells may be helpful to evaluate the involvement of inflammation in various pathologies.

DOI： 10.1080/10715762.2018.1514604

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Resuscitation  

Introduction: The aim of this study was to evaluate the differential effects of mild therapeutic hypothermia (MTH) in post-cardiac arrest syndrome (PCAS) patients depending on the presence/absence of hypoxic encephalopathy (HE) in the early brain CT images obtained before the initiation of MTH. Methods: We conducted a retrospective review of the data of a total of 129 patients with PCAS who were treated by MTH (34 °C) or normothermia treatment (NT) (35 °C or 36 °C), and had undergone brain CT examination prior to the initiation of these treatments. We divided the subjects into 4 groups, namely, the HE(−)/MTH, HE(−)/NT, HE(+)/MTH, and HE(+)/NT groups, for evaluating the interaction effect between the two variables. Then, we compared the neurological outcomes between the HE(−)/MTH and HE(−)/NT groups by multivariate logistic analysis. Good outcome was defined as a Cerebral Performance Category score of ≤2 at 30 days. Results: The percentages of subjects with a good outcome in the HE(−)/MTH and HE(−)/NT group were 68.9% (42/61) and 36.1% (13/36), respectively (p =.003), while those in the HE(+)/MTH and HE(+)/NT groups were lower, at 7.4% (2/27) and 20.0% (1/5), respectively (p =.410), suggesting a statistically significant interaction effect between the two variables (pinteraction = 0.002). In the HE(−) group, MTH was associated with a higher odds ratio of a good outcome as compared to NT (OR 6.80, 95% CI 1.19–38.96, p =.031). Conclusions: The effect of MTH in patients with PCAS differed depending on the presence/absence of evidence of HE on the early CT images.

DOI： 10.1016/j.resuscitation.2018.04.029

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Intensive Care  

Background: The aim of this study is to investigate the association between treatment in a closed ICU and survival at discharge in patients with sepsis. Methods: This is a post hoc analysis utilizing data from the Japan Septic Disseminated Intravascular Coagulation study, including data from patients with sepsis from 2011 to 2013. Multiple logistic regression analysis was used to estimate the association between ICU policy and survival at discharge, and propensity score matching analysis was performed including the same covariates as a sensitivity analysis. Multiple linear regression analysis for the length of ICU stay in surviving patients was also performed with adjustments for the same covariates. Results: Two thousand four hundred ninety-five patients were analyzed. The median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 22 [17-29], the median Sequential Organ Failure Assessment (SOFA) score was 9 [7-12], and the overall mortality was 33%. There were 979 patients treated in 17 open ICUs and 1516 patients in 18 closed ICUs. In comparison, the APACHE II score and SOFA scores were significantly higher in patients in closed ICUs (closed vs open = 23 [18-29] vs 21 [16-28]; p<.001, 9 [7-13] vs 9 [6-12]; p=0.004). There was no difference in the unadjusted mortality (closed vs open; 33.1% vs 33.2%), but in multiple logistic regression analysis, treatment in a closed ICU is significantly associated with survival at discharge (odds ratio=1.59, 95% CI [1.276-1.827], p=.001). The sensitivity analysis (702 pairs of the matching) showed a significantly higher survival rate in the closed ICU (71.8% vs 65.2%, p=0.011). The length of ICU stay of patients in closed ICUs was significantly shorter (20% less). Conclusion: This Japanese nationwide analysis of patients with sepsis shows a significant association between treatment in a closed ICU and survival at discharge, and a 20% decrease in ICU stay.

DOI： 10.1186/s40560-018-0322-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

The aim of this study is to determine the progress of the visual field defects obtained by the Humphrey Field Analyzer 10-2 program (HFA 10-2) in patients with retinitis pigmentosa (RP). The medical records of 45 eyes of 45 RP patients who had at least 3 visual field tests were reviewed. Linear mixed models were used to follow the changes of the mean deviation and the average sensitivity of 4, 12, and 20 points in three concentric squares, designated as S4, S12, and S20. The median follow-up time was 3.86 years [range: 1.93 to 9.86, IQR (Interquartile range): 3.01 to 4.93]. The median number of the visual field tests was 3 (range: 3 to 15, IQR: 3 to 4). The mean change of the MD was -0.46 dB/year (-5.80%/year). When the patients were grouped by the average initial MD, the less advanced group had slower progressions than the more advanced group in S4, S12, and S20. These results should be useful in understanding the pathological changes of RP in the central visual field.

DOI： 10.1038/s41598-017-16640-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(NPO)日本急性血液浄化学会  

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記述言語：日本語   出版者・発行元：(一社)日本農村医学会  

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記述言語：日本語   出版者・発行元：(一社)日本救急医学会  

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