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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. [ABSTRACT FROM AUTHOR]

The goal of this study was to produce a sufficient amount of glutathione in the fermentation medium without the addition of cysteine. This would simplify and reduce the cost of its purification. In addition to reducing the cost of cysteine, it also avoids the inhibition of bacterial growth by cysteine. The gshA, gshB, and cysE genes of Escherichia coli were cloned under the control of the strong T5 promoter of the pQE-80L plasmid and introduced into an E. coli strain knocked out for the genes encoding γ-glutamyltranspeptidase and the GsiABCD glutathione transporter, which are responsible for the recycling of excreted glutathione. The overexpression of the gshA and gshB genes, genes for γ-glutamylcysteine synthetase and glutathione synthetase, and the cysEV95R D96P gene, a gene for serine acetyltransferase with the V95R D96P mutation that makes it insensitive to cysteine, were effective on glutathione production. Na2S2O3 was a good sulfur source for glutathione production, while the addition of Na2SO4 did not affect the glutathione production. With the addition of 50 mM glutamic acid and 75 mM glycine, but without the addition of cysteine, to the simplified SM1 medium, 4.6 mM and 0.56 mM of the reduced and oxidized glutathione, respectively, were accumulated in the extracellular space after 36 h of batch culture. This can eliminate the need to extract glutathione from the bacterial cells for purification. [ABSTRACT FROM AUTHOR]

The spectral energy distribution (SED) of galaxies provides fundamental information on the related physical processes. However, the SED is significantly affected by dust in its interstellar medium. Dust is mainly produced by asymptotic giant branch stars and Type II supernovae. In addition, the dust mass increases through the metal accretion, and the grain size changes by the collisions between the grains. The contribution of each process and the extinction depend on the size distribution. Therefore, the SED model should treat the evolution of the dust mass and size distribution. In spite of the importance of dust evolution, many previous SED models have not considered the evolution of the total mass and size distribution in a physically consistent manner. In this work, we constructed a new radiative transfer SED model, based on our dust evolution model consistent with the chemical evolution. To reduce the computational cost, we adopted the mega-grain and the 1D plane-parallel galaxy approximation. As a fiducial case, we calculated Milky Way-like galaxy SEDs at various ages under the closed-box model. We found that a galaxy at the age of 100 Myr does not produce small grains such as polycyclic aromatic hydrocarbons. After 1 Gyr, we observed a drastic increase of infrared emission and attenuation caused by a rapid increase of dust mass. This phenomenon can be treated appropriately for the first time by our new model. This model can be used for the SED fitting to a galaxy at any stage of evolution. [ABSTRACT FROM AUTHOR]

The influence of the heat transfer field on anomalous film formation under elastohydrodynamic lubrication (EHL) conditions was studied. Liquid lubricant film shapes between a transparent disc and steel ball friction pair were investigated by white light optical interferometry. The fatty alcohol 1-dodecanol was used as the representative lubricant to develop anomalous film shapes. A sapphire disc and glass disc, which have different thermal conductivities, were used as the transparent bounding surface. Experiments were performed wherein the applied load, sliding conditions and ambient temperature were varied. The temperature of the lubricant film was estimated by a simple model with the measured traction coefficient. The estimated temperature and maximum Hertzian pressure were compared with the phase diagram of 1-dodecanol obtained using a diamond anvil cell to investigate the phase state of the lubricant film. It was found that the anomalous film shape was stably formed in the solid-state regime of the phase diagram whereas the film exhibited unique characteristics such as the collapse behaviour in high sliding conditions and liquid-like behaviour of the traction with a remaining thickened film part in the liquid state regime. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Upper limbs cooperative movement functions are very important for us in our everyday life. Due to many kinds of brain diseases, people usually reduced or even lost their half side of body's motion activities, which made it difficult to realize cooperative movements between right and left limbs and in turn greatly reduced their quality of live. In this research, we developed a novel robot system which integrates with virtual reality technologies to perform rehabilitation of upper limbs' cooperative movement functions, such as to realize simultaneous upper limbs' motions or to cooperatively catch and setting a common object in a 3 D work space. Three types of rehabilitation movements are designed so that the subject can train their each arm along as well as cooperative movements in a game style. The motion trajectories as well as the contact forces with objects are automatically recorded which can be used to evaluate the performance of rehabilitation, effectively. [ABSTRACT FROM AUTHOR]

Toward the establishment of the manufacturing process of a novel active airflow control device using atmospheric pressure discharge referred as to dielectric-barrier-discharge (DBD) plasma actuator, a full-inkjet-printed DBD plasma actuator is fabricated for the first time. Printed electronics are superior in view of low-cost process and large area printing compared to photolithography process. Electrodes and dielectric layers are formed by silver nanoparticles-based inks and ultraviolet-curable inks, respectively. Surface observation using a digital microscope reveals the significant improvement of the printing accuracy with an inkjet experimental equipment used in this study compared to that fabricated with a commercially supplied inkjet printer. Electrical and mechanical characteristics of the full-inkjet-printed DBD plasma actuator are evaluated through measurements of discharge current, light emission from surface DBD, and induced flow visualization with particle image velocimetry technique. The results obtained in this study indicate that the fabricated actuator works properly as the active airflow control device using surface DBDs. The full-inkjet-printing process allows the fabrication of a flexible DBD plasma actuator that has an arbitrary electrode shape to induce desirable flow patterns and can be installed on a complex curved surface. [Display omitted] • A flexible full-inkjet-printed dielectric-barrier-discharge (DBD) plasma actuator is fabricated for the first time. • The fabricated DBD plasma actuator works properly as the active airflow control device using surface DBDs. • This method permits to form an arbitrary shape of the actuator to induce desirable flow patterns. [ABSTRACT FROM AUTHOR]

Yessotoxin was isolated from the digestive glands of the scallop, Patinopecten yessoensis , and would be of use as a promising therapeutic tool. We attained the stereoselective construction of KJ ring system of yessotoxin by the intramolecular cyclization of the trisubstituted allylic alcohol using Pd(II) catalyst. [ABSTRACT FROM AUTHOR]

This study investigates the relationship between the molecular structure of lubricants and the appearance of anomalous film shapes in elastohydrodynamic lubrication conditions. A ball-on-disc type test rig was used, which produced a point contact area between a rotating glass disc and rotating steel ball. Several pure liquids such as alkanes, alcohols, and others with a single polar site were used as lubricants. Linear chain lubricants caused solid-like behaviour in the film formation, traction coefficient and flow out time of entrapped lubricant in shock loading tests whereas complexly shaped lubricants caused liquid-like behaviour. The clear dependence on lubricant type appears to indicate that the anomalous film shapes formed due to the solidification of the lubricant. Image 1 • Relationship between anomalous EHL film formation and lubricant type was studied. • EHL tests between a glass disc and a steel ball were conducted. • Pure liquids such as alkanes, alcohols, an acid, an amine and a chloride were tested. • Linear chain lubricants showed solid-like behaviour in film formation and traction. • Complexly shaped lubricants showed liquid-like behaviour. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the associations between individual KRAS, STK11, KEAP1, or TP53 mutations, as well as the comutation status of these genes, and the tumor mutation burden (TMB) with clinical outcomes of lung adenocarcinoma patients treated with immune checkpoint inhibitors (ICIs). Methods: We collected data from patients with lung adenocarcinoma treated with ICIs from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database between June 2019 and August 2023. The main endpoints were the treatment response and overall survival (OS). Results: Among 343 patients with lung adenocarcinoma, 61 (18%), 69 (20%), 41 (12%), and 222 (65%) patients had KRAS, STK11, KEAP1, and TP53 mutations, respectively. An overall objective response was observed in 94 of 338 patients (28%), including 2 (1%) who achieved a complete response and 92 (27%) who achieved a partial response. Patients with STK11, KEAP1, or TP53 mutations had a significantly greater TMB (P<0.001). According to the univariate analysis, the treatment response was significantly correlated with TP53 mutation in both the general (P = 0.041) and KRAS wild-type (P = 0.009) populations. KEAP1 and TP53 mutations were associated with worse OS among assessable patients (hazard ratio (HR) = 2.027, P = 0.002; HR = 1.673, P = 0.007, respectively) and among patients without KRAS mutations (HR = 1.897, P = 0.012; HR = 1.908, P = 0.004, respectively). According to the multivariate analysis, KEAP1 (HR = 1.890, P = 0.008) and TP53 (HR = 1.735, P = 0.011) mutations were found to be independent factors for OS. Conclusions: STK11, KEAP1, and TP53 mutations are significantly associated with a high TMB. TP53 mutation could affect the treatment response to some degree, and both KEAP1 and TP53 mutations resulted in inferior OS in the general patient population and in those with KRAS-wild-type lung adenocarcinoma, indicating that KEAP1 and TP53 mutations might act as prognostic factors for ICI treatment in lung adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the prevalence, risk factors, and clinical outcomes of pulmonary embolism in patients diagnosed with sepsis with and without shock. The National Inpatient Sample was used to identify adults with sepsis with and without shock between 2017 and 2019. The prevalence of acute pulmonary embolism and the association of acute pulmonary embolism with in-hospital mortality, hospital length of stay for survivors, and overall costs of hospitalization were evaluated. Multivariable logistic and linear regression analyses, adjusted for various parameters, were used to explore these associations. Of the estimated 5,019,369 sepsis hospitalizations, 1.2% of patients with sepsis without shock and 2.3% of patients with septic shock developed pulmonary embolism. The odds ratio for in-hospital mortality was 1.94 (95% confidence interval (CI) 1.85–2.03, p < 0.001). The coefficient for hospital length of stay was 3.24 (95% CI 3.03–3.45, p < 0.001). The coefficient for total costs was 46,513 (95% CI 43,079–49,947, p < 0.001). The prevalence of pulmonary embolism in patients diagnosed with sepsis with and without shock was 1.2 and 2.3%, respectively. Acute pulmonary embolism was associated with higher in-hospital mortality, longer hospital length of stay for survivors, and higher overall costs of hospitalization. [ABSTRACT FROM AUTHOR]

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 (pinteraction = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer. Methods: Preoperative DCF (docetaxel, 70 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; fluorouracil, 750 mg/m2/day, days 1–5) was repeated every 3 weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients. Results: According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3′-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027). Conclusions: ABCC2-24C > T (rs717620), TYMS 3′-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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%; I 2 = 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; I 2 = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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) ng·h/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) ng·h/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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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%. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ΔDIC score as ((DIC score on Day 3) − (DIC score on Day 1)). The primary outcome was to determine whether the predictive accuracy of ΔDIC was more than 0. The secondary outcome was the actual predictive accuracy of ΔDIC (predicted ΔDIC−real ΔDIC). 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 ΔDIC and real ΔDIC 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ionic single crystals of the polyoxometalate [MoV2MoVI16O54(SO3)2]6– salted with tetrabutylammonium were found to exhibit dielectric anomalies at 235 and 302 K. The clear DSC peak at 235 K indicates the first‐order nature of transition. The next transition at 302 K was concluded to be second‐order in nature, demonstrating the existence of three different phases (α, β, and γ). Temperature‐dependent single‐crystal X‐ray diffraction analysis revealed that the structural phase transitions occur owing to orientational changes in the structures of the cation alkyl chains and the crystalline solvent of acetonitrile where the structure of Mo18 polyoxometalate was comparable. The polymorphous and flexible configuration of the alkyl chains was reasoned to be the origin of the temperature dependence of the structure. Ionic single crystals of the polyoxometalate [MoV2MoVI16O54(SO3)2]5– salted with tetrabutylammonium were found to exhibit thermal and dielectric anomalies at 235 and 302 K. Temperature‐dependent single‐crystal X‐ray diffraction analysis revealed that the structural phase transitions occur owing to changes in the structures of the cation alkyl chains. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

On temperate and tropical shores around the world, a guild of sacoglossan opisthobranchs associates with filamentous green algae. This guild of four genera in three different families (Hermaeidae: Aplysiopsis; Limapontiidae: Ercolania, Limapontia; Plakobranchidae: Elysia) has been well studied in many geographical regions. Despite detailed information for Hong Kong, there is comparatively little information for Japanese shores. From 2000 to 2010, this guild of sacoglossans was investigated in two regions of Japan. On the Pacific shores of Honshu, Japan, at least ten species occupy this guild including Aplysiopsis minor, A. toyamana, A. nigra, A. orientalis, Ercolania boodleae, E. subviridis, Elysia hamatanii and E. abei. Two described species (Elysia nigrocapitata and E. hirasei) were not recorded but also occupy this temperate guild in Japan. On the west-coast shores of Okinawa (East China Sea), at least three species occur in this guild: Ercolania subviridis and two undescribed or unrecognized species of Ercolania. We quantified the size–frequency and abundance of specimens, characterized their spawn masses, and conducted feeding preference experiments. Many of the sacoglossans were seasonally frequent to abundant, their feeding activities were concentrated on uniseriate filaments of green algae (Order Cladophorales: Family Cladophoraceae and/or Order Siphonocladales: Family Boodleaceae), and their larvae were typically planktotrophic; yet, many of these species are regional endemics. Our results complement the wealth of ecological information available for other, more depauperate geographical regions. [ABSTRACT FROM AUTHOR]

B Introduction: b Sedation is an essential component of critical care for patients undergoing mechanical ventilation. Thus, this systematic review and meta-analysis aimed to clarify whether treatment with dexmedetomidine could reduce the mortality on top of intensive care unit length of stay, and ventilator-free days in patients with sepsis. However, more recent large randomized-controlled trials (RCTs) in patients with sepsis reported that dexmedetomidine use was not associated with improved outcomes (Shehabi et al. 2019 and Hughes et al. 2021). [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]