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This study identified the most accurate model for predicting longitudinal craniofacial growth in a Japanese population using statistical methods and machine learning. Longitudinal lateral cephalometric radiographs were collected from 59 children (27 boys and 32 girls) with no history of orthodontic treatment. Multiple regression analysis, least absolute shrinkage and selection operator, radial basis function network, multilayer perceptron, and gradient-boosted decision tree were used. The independent variables included 26 coordinated values of skeletal landmarks, 13 linear skeletal parameters, and 17 angular skeletal parameters in children ages 6 to 12 years. The dependent variables were the values of the 26 coordinated skeletal landmarks, 13 skeletal linear parameters, and 17 skeletal angular parameters at 13 years of age. The difference between the predicted and actual measured values was calculated using the root-mean-square error. The prediction model for craniofacial growth using the least absolute shrinkage and selection operator had the smallest average error for all values of skeletal landmarks, linear parameters, and angular parameters. The highest prediction accuracies when predicting skeletal linear and angular parameters for 13-year-olds were 97.87% and 94.45%, respectively. This model incorporates several independent variables and is useful for future orthodontic treatment because it can predict individual growth. [ABSTRACT FROM AUTHOR]

The article presents the case study of two cases of anomalous systemic arterial supply to the basal segment of the left lung in infants. It emphasizes the importance of balloon occlusion pulmonary angiography for accurate diagnosis and surgical planning. It is reported that the congenital anomaly involves abnormal systemic arterial branches supplying normal lung segments.

Therapeutic hypothermia (TH) for severe traumatic brain injury has seen restricted application due to the outcomes of randomized controlled trials (RCTs) conducted since 2000. In contrast with earlier RCTs, recent trials have implemented active normothermia management in control groups, ensuring comparable intensities of non-temperature-related therapeutic interventions, such as neurointensive care. This change in approach may be a contributing factor to the inability to establish the efficacy of TH. Currently, an active temperature management method using temperature control devices is termed "targeted temperature management (TTM)". One of the goals of TTM for severe traumatic brain injury is the regulation of increased intracranial pressure, employing TTM as a methodology for intracranial pressure management. Additionally, fever in traumatic brain injury has been acknowledged as contributing to poor prognosis, underscoring the importance of proactively preventing fever. TTM is also employed for the preemptive prevention of fever in severe traumatic brain injury. As an integral component of current neurointensive care, it is crucial to precisely delineate the targets of TTM and to potentially apply them in the treatment of severe traumatic brain injury. [ABSTRACT FROM AUTHOR]

To develop a vaccine against Toxoplasma gondii, a vaccine antigen with immune-stimulating activity is required. In the present study, we investigated the immunogenicity and prophylactic potential of T. gondii peroxiredoxin 1 (TgPrx1). The TgPrx1 was detected in the ascitic fluid of mice 6 days postinfection, while specific antibody levels were low in the sera of chronically infected mice. Treatment of murine peritoneal macrophages with recombinant TgPrx1 triggered IL-12p40 and IL-6 production, but not IL-10 production. In response to TgPrx1, activation of NF-kB and IL-6 production were confirmed in mouse macrophage cell line (RAW 264.7). These results suggest the immune-stimulating potentials of TgPrx1. Immunization of mice with recombinant TgPrx1 stimulated specific antibody production (IgG1 and IgG2c). Moreover, spleen cell proliferation and interferon-gamma production significantly increased in the TgPrx1- sensitized cells from mice immunized with the same antigen. Immunization with TgPrx1 also increased mouse survival and decreased cerebral parasite burden against lethal T. gondii infection. Thus, our results suggest that TgPrx1 efficiently induces humoral and cellular immune responses and is useful as a new vaccine antigen against toxoplasmosis. [ABSTRACT FROM AUTHOR]

Background Recent studies have focused on the association between plasma electrolytes, particularly potassium level and neurologic outcomes in patients with traumatic brain injury (TBI). We hypothesized that potassium level on admission is an indicator for initiation of targeted temperature management in patients with severe TBI. Methods We re-evaluated the Brain Hypothermia Study data based on the potassium levels on admission (i.e., hypokalemia [<3.5 mEq/L] or normokalemia [3.5–5 mEq/L]) and compared these values and Glasgow Outcome Scale scores at 6 months by per protocol analysis. Consequently, 135 patients were enrolled. Finally, groups 50 and 23 patients with hypokalemia and 34 and 23 patients with normokalemia were allocated to mild therapeutic hypothermia (MTH) and fever control groups, respectively. Baseline characteristics, complication rates, and favorable neurologic outcome rates were compared between the two groups. Results In the normokalemia patients, fever control management was associated with a significant increase in favorable neurologic outcome compared with those in the MTH group (68.2% vs. 35.3%; P = 0.03). The complication rate was significantly higher in the MTH group than in the fever control group for patients with normokalemia (23.4% vs. 0%; P = 0.03). Conversely, hypokalemia patients in the MTH group revealed relatively better favorable neurologic outcomes compared with those in the fever control group (52.0% vs. 39.1%; P = 0.33). Conclusions The initial potassium level may be an indicator in determining appropriate targeted temperature management for patients with TBI. Fever control may be considered instead of MTH for normokalemia patients with TBI on admission. [ABSTRACT FROM AUTHOR]

Yttria-stabilized zirconia (YSZ) consists of zirconia and yttria and oxygen vacancies appear in accordance with the ratio of yttria. The oxygen vacancy would sometimes give annoyance, but it would be beneficial on other occasions, depending on its applications. Photoluminescence (PL) due to oxygen vacancies induced by photons with energies around 5.5 eV exhibits two decay time constants. As a possible reason for this, an oxygen vacancy changes its charging state from neutral to positive monovalent by losing an electron when YSZ is irradiated by ultraviolet photons. The PL decays either in a ms range or in a ns range, depending on whether the oxygen vacancies are neutral or positive monovalent. [ABSTRACT FROM AUTHOR]

Hypothesis Although the interaction of DNA with various types of intercalating chemicals, such as planar polycyclic aromatic compounds, has been extensively investigated over the past several decades, little is known about the relationship between the structure of a DNA binder and its affinity for DNA. The use of DNA as an adsorbent for environmental cleaning purposes requires information on its affinity for organic chemicals with different structures. Experiment In the present study we investigated the binding of DNA to aromatic chemicals with various structures and charges by three methods: binding of organic chemicals to DNA followed by removal by precipitation with cationic nanoparticles (1) or a cationic surfactant (2), and absorption of organic chemicals by a DNA hydrogel (3). Findings The results showed that, for most neutral organic chemicals, the hydrophobicity of the organic molecule is the main driving force for efficient binding to DNA. The double-helicity of DNA contributed to stronger binding to most of the compounds. The efficiency of the uptake of organic chemicals increased substantially when a hydrophobic cationic surfactant was used for DNA-complex condensation and removal. The potential environmental application of DNA as an adsorbent for the removal of aromatic organic pollutants from water is discussed. [ABSTRACT FROM AUTHOR]

We present the availability of a fluorous solvent, 1,1,1,2,3,4,4,5,5,5-decafluoropentane (C5F10), for the non-aqueous medium in liquid-liquid electrochemistry. The solvent is immiscible, and forms stable interface with water (W). The solvent dissolved a high concentration of a hydrophobic electrolyte, tetrabutylammonium bis(nona fluorobutanesulfonyl)imide (TBABNSI), and the TBABNSI (C5F10) solution gave a high conductivity. The TBABNSI (C5F10)| LiCl (W) interface gave a polarizable potential window. Within the potential window, tetramethylammonium ion gave a reversible voltammetric wave due to its transfer across the C5F10 | W interface. The potential window became wider by replacement of the supporting electrolytes in C5F10- and W-phases. The results indicate that various ion-transfer reactions at the C5F10 | W interface can be studied voltammetrically. [ABSTRACT FROM AUTHOR]

Background: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time and outcomes in accidental hypothermia (AH) patients compared to those of patients without AH has not been fully investigated. Methods: This was a secondary analysis of the retrospective multicenter registry in Japan. We enrolled patients aged ≥ 18 years who had been admitted to the emergency department for OHCA and had undergone ECPR between January, 2013 and December, 2018. AH was defined as an arrival body temperature below 32 °C. The primary outcome was survival to discharge. Cubic spline analyses were performed to assess the non-linear associations between low-flow time and outcomes stratified by the presence of AH. We also analyzed the interaction between low-flow time and the presence of AH. Results: Of 1252 eligible patients, 105 (8.4%) and 1147 (91.6%) were in the AH and non-AH groups, respectively. Median low-flow time was 60 (47–79) min in the AH group and 51 (42–62) min in the non-AH group. The survival discharge rates in the AH and non-AH groups were 44.8% and 25.4%, respectively. The cubic spline analyses showed that survival discharge rate remained constant regardless of low-flow time in the AH group. Conversely, a decreasing trend was identified in the survival discharge rate with longer low-flow time in the non-AH group. The interaction analysis revealed a significant interaction between low-flow time and AH in survival discharge rate (p for interaction = 0.048). Conclusions: OHCA patients with arrival body temperature < 32 °C who had received ECPR had relatively good survival outcomes regardless of low-flow time, in contrast to those of patients without AH. [ABSTRACT FROM AUTHOR]

The article presents a case study of a female neonate with right pulmonary agenesis and severe tracheomalacia. It is reported that the patient initially showed no airway problems in the neonatal period but developed severe ventilatory insufficiency at four months of age. It is further reported that enhanced CT revealed severe mediastinal distortion and tracheal compression by the aorta.

Recently, patients with out-of-hospital cardiac arrest (OHCA) refractory to conventional resuscitation have started undergoing extracorporeal cardiopulmonary resuscitation (ECPR). However, the mortality rate of these patients remains high. This study aimed to clarify whether a center ECPR volume was associated with the survival rates of adult patients with OHCA resuscitated using ECPR. This was a secondary analysis of a retrospective multicenter registry study, the SAVE-J II study, involving 36 participating institutions in Japan. Centers were divided into three groups according to the tertiles of the annual average number of patients undergoing ECPR: high-volume (≥ 21 sessions per year), medium-volume (11–20 sessions per year), or low-volume (< 11 sessions per year). The primary outcome was survival rate at the time of discharge. Patient characteristics and outcomes were compared among the three groups. Moreover, a multivariable-adjusted logistic regression model was applied to study the impact of center ECPR volume. A total of 1740 patients were included in this study. The center ECPR volume was strongly associated with survival rate at the time of discharge; furthermore, survival rate was best in high-volume compared with medium- and low-volume centers (33.4%, 24.1%, and 26.8%, respectively; P = 0.001). After adjusting for patient characteristics, undergoing ECPR at high-volume centers was associated with an increased likelihood of survival compared to middle- (adjusted odds ratio 0.657; P = 0.003) and low-volume centers (adjusted odds ratio 0.983; P = 0.006). The annual number of ECPR sessions was associated with favorable survival rates and lower complication rates of the ECPR procedure. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr%5fe/ctr%5fview.cgi?recptno=R000041577 (unique identifier: UMIN000036490). [ABSTRACT FROM AUTHOR]

A better understanding of the relative contributions of various factors to patient outcomes is essential for optimal patient selection for extracorporeal CPR (ECPR) therapy for patients with out-of-hospital cardiac arrest (OHCA). However, evidence on the prognostic comparison based on the etiologies of cardiac arrest is limited. What is the etiology-based prognosis of patients undergoing ECPR for OHCA? This retrospective multicenter registry study involved 36 institutions in Japan and included all adult patients with OHCA who underwent ECPR between January 2013 and December 2018. The primary etiology for OHCA was determined retrospectively from all hospital-based data at each institution. We performed a multivariable logistic regression model to determine the association between etiology of cardiac arrest and two outcomes: favorable neurologic outcome and survival at hospital discharge. We identified 1,781 eligible patients, of whom 1,405 (78.9%) had cardiac arrest because of cardiac causes. Multivariable logistic regression analysis for favorable neurologic outcome showed that accidental hypothermia (adjusted OR, 5.12; 95% CI, 2.98-8.80; P <.001) was associated with a significantly higher rate of favorable neurologic outcome than cardiac causes. Multivariable logistic regression analysis for survival showed that accidental hypothermia (adjusted OR, 5.19; 95% CI, 3.15-8.56; P <.001) had significantly higher rates of survival than cardiac causes. Acute aortic dissection/aneurysm (adjusted OR, 0.07; 95% CI, 0.02-0.28; P <.001) and primary cerebral disorders (adjusted OR, 0.12; 95% CI, 0.03-0.50; P =.004) had significantly lower rates of survival than cardiac causes. In this retrospective multicenter cohort study, although most patients with OHCA underwent ECPR for cardiac causes, accidental hypothermia was associated with favorable neurologic outcome and survival; in contrast, acute aortic dissection/aneurysm and primary cerebral disorders were associated with nonsurvival compared with cardiac causes. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: In some cases of patients with out-of-hospital cardiac arrest (OHCA) who underwent extracorporeal cardiopulmonary resuscitation (ECPR), negative pupillary light reflex (PLR) and mydriasis upon hospital arrival serve as common early indicator of poor prognosis. However, in certain patients with poor prognoses inferred by pupil findings upon hospital arrival, pupillary findings improve before and after the establishment of ECPR. The association between these changes in pupillary findings and prognosis remains unclear. This study aimed to clarify the association of pupillary examinations before and after the establishment of ECPR in patients with OHCA showing poor pupillary findings upon hospital arrival with their outcomes. To this end, we analysed retrospective multicentre registry data involving 36 institutions in Japan, including all adult patients with OHCA who underwent ECPR between January 2013 and December 2018. We selected patients with poor prognosis inferred by pupillary examinations, negative pupillary light reflex (PLR) and pupil mydriasis, upon hospital arrival. The primary outcome was favourable neurological outcome, defined as Cerebral Performance Category 1 or 2 at hospital discharge. Multivariable logistic regression analysis was performed to evaluate the association between favourable neurological outcome and pupillary examination after establishing ECPR. Results: Out of the 2,157 patients enrolled in the SAVE-J II study, 723 were analysed. Among the patients analysed, 74 (10.2%) demonstrated favourable neurological outcome at hospital discharge. Multivariable analysis revealed that a positive PLR at ICU admission (odds ration [OR] = 11.3, 95% confidence intervals [CI] = 5.17–24.7) was significantly associated with favourable neurological outcome. However, normal pupil diameter at ICU admission (OR = 1.10, 95%CI = 0.52–2.32) was not significantly associated with favourable neurological outcome. Conclusion: Among the patients with OHCA who underwent ECPR and showed poor pupillary examination findings upon hospital arrival, 10.2% had favourable neurological outcome at hospital discharge. A positive PLR after the establishment of ECPR was significantly associated with favourable neurological outcome. [ABSTRACT FROM AUTHOR]

The prognosis for patients with out-of-hospital cardiac arrest (OHCA) has been reported to be worse in the cold season. On the other hand, it is unclear whether a similar trend exists in OHCA patients who are treated with extracorporeal cardiopulmonary resuscitation (ECPR). This study was a retrospective multicenter registry study. We examined the association between ECPR and season. We compared the prognosis in four seasonal groups according to the day of occurrence. Multivariable logistic regression analysis was performed for the assessment of clinical and neurological outcomes. A total of 2024 patients with OHCA who received ECRP were included. There were no significant differences in in-hospital mortality (p = 0.649) and in the rate of favorable neurological outcome (p = 0.144). In the multivariable logistic regression, the seasonal factor was not significantly associated with worse in-hospital mortality (p = 0.855) and favorable neurological outcomes (p = 0.807). In this study, there was no seasonal variation in OHCA patients with ECPR. [ABSTRACT FROM AUTHOR]

B Learning Objectives: b The importance of Neurocritical care (NCC) has been recognized. Moreover, after the seminars, 72 (97.3%) participants were satisfied with them, and the numbers of professionals who could not felt NCC confident decreased from 28 (37.8%) before the seminar to 1(1.35%) after its completion (p<0.001). B Conclusions: b Our seminar successfully improved the physician's knowledges of NCC after its completion, and satisfied them with more confidence in NCC. [Extracted from the article]

Background: Bleeding is the most common complication in out-of-hospital cardiac arrest (OHCA) patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). No studies comprehensively described the incidence rate, timing of onset, risk factors, and treatment of bleeding complications in OHCA patients receiving ECPR in a multicenter setting with a large database. This study aimed to analyze the risk factors of bleeding during the first day of admission and to comprehensively describe details of bleeding during hospitalization in patients with OHCA receiving ECPR in the SAVE-J II study database. Methods: This study was a secondary analysis of the SAVE-J II study, which is a multicenter retrospective registry study from 36 participating institutions in Japan in 2013–2018. Adult OHCA patients who received ECPR were included. The primary outcome was the risk factor of bleeding complications during the first day of admission. The secondary outcomes were the details of bleeding complications and clinical outcomes. Results: A total of 1,632 patients were included. Among these, 361 patients (22.1%) had bleeding complications during hospital stay, which most commonly occurred in cannulation sites (14.3%), followed by bleeding in the retroperitoneum (2.8%), gastrointestinal tract (2.2%), upper airway (1.2%), and mediastinum (1.1%). These bleeding complications developed within two days of admission, and 21.9% of patients required interventional radiology (IVR) or/and surgical interventions for hemostasis. The survival rate at discharge of the bleeding group was 27.4%, and the rate of favorable neurological outcome at discharge was 14.1%. Multivariable logistic regression analysis showed that the platelet count (< 10 × 104/μL vs > 10 × 104/μL) was significantly associated with bleeding complications during the first day of admission (adjusted odds ratio [OR]: 1.865 [1.252–2.777], p = 0.002). Conclusions: In a large ECPR registry database in Japan, up to 22.1% of patients experienced bleeding complications requiring blood transfusion, IVR, or surgical intervention for hemostasis. The initial platelet count was a significant risk factor of early bleeding complications. It is necessary to lower the occurrence of bleeding complications from ECPR, and this study provided an additional standard value for future studies to improve its safety. [ABSTRACT FROM AUTHOR]

Background: Aneurysmal subarachnoid hemorrhage is a life-threatening disease requiring neurocritical care. Delayed cerebral ischemia is a well-known complication that contributes to unfavorable neurological outcomes. Cerebral vasospasm has been thought to be the main cause of delayed cerebral ischemia, and although several studies were able to decrease cerebral vasospasm, none showed improved neurological outcomes. Our target is not cerebral vasospasm but improving neurological outcomes. The purpose of this review is to discuss what intensivists should know and can do to improve clinical outcomes in subarachnoid hemorrhage patients. Delayed cerebral ischemia is thought to be due to not only vasospasm but also multifactorial mechanisms. Additionally, the concept of early brain injury, which occurs within the first 72 h after the hemorrhage, has become an important concern. Increasing sympathetic activity after the hemorrhage is associated with cardiopulmonary complications and poor outcomes. Serum lactate measurement may be a valuable marker reflecting the severity of sympathetic activity. The transpulmonary thermodilution method will bring about an advanced understanding of hemodynamic management. Fever is a well-recognized symptom and targeted temperature management is an anticipated intervention. To avoid hyperglycemia and hypoglycemia, performing moderate glucose control and minimizing glucose variability are important concepts in glycemic management, but the optimal target range remains unknown. Dysnatremia seems to be associated with negative outcomes. It is not clear yet that maintaining normonatremia actively improves neurological outcomes. Optimal duration of intensive care management has not been determined. Short conclusion: Although we have an advanced understanding of the pathophysiology and clinical characteristics of subarachnoid hemorrhage, there are many controversies in the intensive care unit management of subarachnoid hemorrhage. With an awareness of not only delayed cerebral ischemia but also early brain injury, more attention should be given to various aspects to improve neurological outcomes. [ABSTRACT FROM AUTHOR]

Highlights • NcCyp-OML activated NF-κB signaling. • NcCyp-OML triggered IL-12p40 production from macrophages. • NcCyp-OML induced antigen-specific humoral and cellular immunity. • NcCyp-OML protected mice against Neospora infection. • TLR2 was required for the protective efficacy induced by NcCyp-OML. Abstract Neospora caninum is an intracellular protozoan parasite closely related to Toxoplasma gondii. N. caninum is thought to be a major cause of abortion in cattle worldwide. Given the current situation of drastic economic losses and a lack of efficient control strategies against such parasites, the challenge to develop potent vaccine candidates and technologies remains. We investigated the immune stimulating activity of N. caninum cyclophilin (NcCyp) with and without a formulation with oligomannose-coated-liposomes (OML) as the potential adjuvant. NcCyp-OML activated NF-κB in RAW 264.7 cells and triggered interleukin (IL)-12p40 production from murine peritoneal macrophages. In BALB/c mice, immunization with NcCyp-OML was associated with the production of specific antibodies (IgG1 and IgG2a). The specific antibody (IgG1) against naked NcCyp was also observed after the challenge infection, but it was significantly lower than those of NcCyp-OML. Moreover, significant cellular immune responses were induced, including spleen cell proliferation and interferon-gamma production. The immunization of mice with NcCyp-OML, and to lesser extent with naked NcCyp, induced significant protection against challenge with a lethal dose of N. caninum compared with the PBS control group. This protection was associated with a higher survival rate, slight changes in body weight, and lower clinical score of mice. In addition, the significant protective efficacy of NcCyp-OML was confirmed in another mouse strain, male C57BL/6 mice. The current study revealed the marked contribution of Toll-like receptor 2 (TLR2) to the protective immunity triggered by NcCyp-OML because higher numbers of TLR2−/− mice succumbed to a lethal dose of N. caninum compared with C57BL/6 mice. Moreover, prominent spleen cell proliferation and IFN-γ production was induced in NcCyp-OML-immunized mice by a TLR2-dependent mechanism. [ABSTRACT FROM AUTHOR]

Background: Little is known about the natural history of comatose patients with brain injury, as in many countries most of these patients die in the context of withdrawal of life-sustaining therapies (WLSTs). The accuracy of predicting recovery that is used to guide goals-of-care decisions is uncertain. We examined long-term outcomes of patients with ischemic or hemorrhagic stroke predicted by experienced clinicians to have no chance of meaningful recovery in Japan, where WLST in patients with isolated neurological disease is uncommon. Methods: We retrospectively reviewed the medical records of all patients admitted with acute ischemic stroke, intracerebral hemorrhage, or nontraumatic subarachnoid hemorrhage between January 2018 and December 2020 to a neurocritical care unit at Toda Medical Group Asaka Medical Center in Saitama, Japan. We screened for patients who were predicted by the attending physician on postinjury day 1–4 to have no chance of meaningful recovery. Primary outcome measures were disposition at hospital discharge and the ability to follow commands and functional outcomes measured by the Glasgow Outcome Scale-Extended (GOS-E), which was assessed 6 months after injury. Results: From 860 screened patients, we identified 40 patients (14 with acute ischemic stroke, 19 with intracerebral hemorrhage, and 7 with subarachnoid hemorrhage) who were predicted to have no chance of meaningful recovery. Median age was 77 years (interquartile range 64–85), 53% (n = 21) were women, and 80% (n = 32) had no functional deficits prior to hospitalization. Six months after injury, 17 patients were dead, 14 lived in a long-term care hospital, 3 lived at home, 2 lived in a rehabilitation center, and 2 lived in a nursing home. Three patients reliably followed commands, two were in a vegetative state (GOS-E 2), four fully depended on others and required constant assistance (GOS-E 3), one could be left alone independently for 8 h per day but remained dependent (GOS-E 4), and one was independent and able to return to work-like activities (GOS-E 5). Conclusions: In the absence of WLST, almost half of the patients predicted shortly after the injury to have no chance of meaningful recovery were dead 6 months after the injury. A small minority of patients had good functional recovery, highlighting the need for more accurate neurological prognostication. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to examine whether the temperature difference between the jugular bulb and pulmonary artery (ΔTjb-pa) is associated with the neurological outcome of patients with severe traumatic brain injury (TBI). Methods: We conducted a post hoc analysis of a multicenter randomized controlled trial of mild therapeutic hypothermia (TH, 32.0–34.0°C) or fever control (FC, 35.5–37.0°C) for the patients with severe TBI. ΔTjb-pa averaged every 12 h and the variation in ΔTjb-pa were compared between patients with favorable (n = 39) and unfavorable (n = 37) neurological outcomes. These values were also compared in the TH and FC subgroups. Results: The average ΔTjb-pa values in patients with favorable and unfavorable outcomes were 0.24 ± 0.23 and 0.06 ± 0.36°C, respectively (P < 0.001). ΔTjb-pa trended significantly higher in the favorable outcome patients than in the unfavorable outcome patients throughout the 120 h after onset of severe TBI (P < 0.001). The variation in ΔTjb-pa from 0 to 72 h was significantly lower in the favorable outcome patients than in the unfavorable outcome patients (0.8 ± 0.8 vs 1.8 ± 2.5°C, respectively, P = 0.013). From 72 to 120 h, there was no significant difference in the variation in ΔTjb-pa. Significant differences between patients with favorable and unfavorable outcomes in ΔTjb-pa and the variation in ΔTjb-pa were similar in the TH subgroup, but not evident in the FC subgroup. Conclusions: A reduction in ΔTjb-pa and greater variation in ΔTjb-pa were associated with an unfavorable outcome in patients with severe TBI, especially those treated with TH. When treating severe TBI patients, it is important to understand that there will be differences in temperature reflecting the brain environment and the systemic temperature, depending on the severity and outcome of TBI during TH. [ABSTRACT FROM AUTHOR]

We examined the partition of two amines, procaine and metoprolol, in ionic and charge-neutral forms between organic solvent (O) 1,2-dichloroethane and water (W) phases, each of which contained a common ion, [(C n F 2n+1 SO 2 ) 2 N] − , as tetrabutylammonium and Li + salts, respectively, to control the potential difference at the O|W interface, Δ O W ϕ. The interfacial system would be useful in the study of the partitioning of ionic species, which depends on Δ O W ϕ. With different pH levels, the dependence of the distribution ratio on Δ O W ϕ satisfied the prediction from the theoretical equation, giving the formal potentials for the transfer of the ionic forms at the O|W interface. We also examined the partition of nourseothricin, a mixture of streptothricin antibiotics with different sizes of lysine oligomers. They would exist as di-, tri-, tetra- and pentavalent cations in fully protonated forms. The distribution ratio for each ionic species could be determined simultaneously using an HPLC technique. The dependence of the distribution ratio on Δ O W ϕ for each species also satisfied the prediction, giving their formal potentials. Therefore, the present interfacial system can be applied when both ionic and charge-neutral species are partitioned and when the sample is of low purity or is a mixture. [ABSTRACT FROM AUTHOR]

Oligomannose-coated liposomes (OMLs), containing entrapped antigens, serve as effective antigen delivery vehicles and as a novel adjuvant to induce antigen-specific cellular immune responses. However, in vitro activation of antigen-presenting cells (APCs) by OMLs has not yet been demonstrated. In this paper, we found that OMLs can deliver the antigens and the stimulatory signals into inflammatory monocytes in vitro , leading to differentiation of the cells to mature APCs. When OMLs were co-cultured with peripheral blood mononuclear cells from C57BL/6 mice in the presence of mouse serum, OMLs were preferentially incorporated into both Ly6C high monocytes and Ly6C low monocytes, which are referred to as murine inflammatory and resident monocytes, respectively. The expression of CD11c, CD80, CD86, CCR7, and MHC class II on the Ly6C high monocytes was significantly enhanced during the 24 h after OML uptake, whereas upregulation of these molecules on the Ly6C low monocytes was limited. In addition, the antigenic peptide of OVA encased in OMLs was presented on MHC class I of only Ly6C high monocytes. Furthermore, OVA-encasing OML-ingesting monocytes can activate CD8 + T cells from OT-1 mice, suggesting that antigens encapsulated in OMLs were cross-presented in inflammatory monocytes. Adoptive transfer of the monocytes that engulf OVA-encasing OMLs led to induction of an antigen-specific Th1 immune response in mice. Taken together, mature APCs can be generated from inflammatory monocytes in peripheral blood by ex vivo treatment of the cells with OMLs without any additional stimuli. [ABSTRACT FROM AUTHOR]

Ion-transfer reactions at the interface between fluorous solvent 1,1,1,2,3,4,4,5,5,5-decafluoropentane (DFP) and water (W) were investigated voltammetrically. Within the potential window at the DFP | W interface, various non-fluorinated ions, including tetraphenylarsonium and tetraphenylborate, and fluorinated ions, including fluorocomplex and perfluoro- n -alkanoate ions, gave reversible voltammetric waves for their ion transfer across the DFP | W interface. Based on the tetraphenylarsonium-tetraphenylborate assumption, the formal potentials of their ion transfer could be determined in terms of the Galvani potential difference. Also, formal potentials for the transfer of bis(perfluoroalkanesulfonyl)imide ions at the DFP | W interface were determined potentiometrically. The formal Gibbs energies for the transfer of ions from DFP to W, which would provide the criteria necessary for evaluating the fluorophilicity/hydrophilicity of ions were calculated from the formal potentials, and were compared with the transfer energies from 1,2-dichloroethane to W and those from the organic solvent to DFP, as quantitative scales of the ions' lipophilicity/hydrophilicity and fluorophilicity/lipophilicity. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effect of the potential interaction between sepsis and acute respiratory distress syndrome (ARDS) on the 6-month clinical outcomes. Methods: This secondary analysis of a prospective multicenter observational study included patients who were expected to receive mechanical ventilation for more than 48 h. Patients were stratified based on the incidence of sepsis and further subdivided according to the presence of ARDS. The primary endpoints for patients whose follow-up information was available included mortality (n = 162) and the occurrence of PICS (n = 96) at six months. The diagnosis of PICS was based on any of the following criteria: (1) decrease ≥ 10 points in the physical component score of the 36-item Short Form (SF36) questionnaire; (2) decrease ≥ 10 points in the mental component score of the SF-36; or (3) decline in the Short Memory Questionnaire (SMQ) score and SMQ score < 40 at six months after ICU admission. We conducted multivariate logistic regression analyses to assess the effect of the potential interaction between ARDS and sepsis on the 6-month clinical outcomes. Results: The mortality in the ARDS sub-group was higher than that in the non-ARDS subgroup [47% (7/15) versus 21% (18/85)] in the non-sepsis group. However, the mortality in the ARDS and non-ARDS subgroups was similar in the sepsis group. Multivariate logistic regression analyses revealed that ARDS was significantly associated with mortality in the non-sepsis group (adjusted OR: 5.25; 95% CI: 1.45-19.09; p =.012), but not in the sepsis group (P for interaction =.087). Multivariate logistic regression analyses showed ARDS was not associated with PICS occurrence in the non-sepsis and sepsis groups (P-value for the interaction =.039). Conclusions: This hypothesis-generating study suggested that the effect of ARDS on the 6-month outcomes depended on the presence or absence of sepsis. Trial registration: Not applicable [ABSTRACT FROM AUTHOR]

A1C-derived individualized glycemic management is currently more suitable for patients with A1C above 7.4% than those with A1C below 7.4%. If we could treat patients with low target glucose levels without any hypoglycemia, there might still be room to improve their outcomes. The negative impact of hypoglycemia observed in patients with lower A1C may have obscured the potential benefit of individualized management for those with a higher A1C. [Extracted from the article]

The aim of this single-center retrospective study was to investigate the association between the time in range (TIR) of relative normoglycemia (RN) and in-hospital mortality. We defined RN as measured blood glucose in the range of 70–140% of A1C-derived average glucose and absolute normoglycemia (AN) as 70–140 mg/dL. We conducted multivariate logistic regression analyses to examine the association between TIR of RN > 80% or TIR of AN > 80% up to 72 h after ICU admission and in-hospital mortality (Model 1 and Model 2, respectively). The discrimination of the models was assessed using the area under the receiver operating characteristic curve (AUROC). Among 328 patients, 35 died in hospital (11%). Model 1 showed that TIR of RN > 80% was associated with reduced in-hospital mortality (adjusted OR 0.16; 95% CI 0.06–0.43; P < 0. 001); however, Model 2 showed that the TIR of AN > 80% was not. The AUROC of Model 1 was significantly higher than that of Model 2 (0.84 [95% CI 0.77–0.90] vs. 0.79 [0.70–0.87], P = 0.008).Our findings provide a foundation for further studies exploring individualized glycemic management in ICUs. [ABSTRACT FROM AUTHOR]

Background: Hypothermia is neuroprotective in some ischemia-reperfusion injuries. Ischemia-reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia-reperfusion injury and improve global neurologic outcome.Methods: This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels.Results: Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups.Conclusions: This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups. [ABSTRACT FROM AUTHOR]

This study evaluated the association between intra-aortic balloon pump (IABP) use in patients with out-of-hospital cardiac arrest (OHCA) caused by acute coronary syndrome (ACS) who received extracorporeal cardiopulmonary resuscitation (ECPR) and 30-day outcomes. This study was a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter registry study involving 36 participating institutions in Japan. Patients with cardiac arrest caused by ACS who received ECPR were divided into two groups depending on whether or not they received IABP. The primary outcome was 30-day survival. Subgroup analysis was performed to detect what type of patients were mostly associated with improved outcomes. Of 2,157 patients registered in the SAVE-J II study, 877 patients were enrolled in this study, 702 patients in the IABP group and 175 patients in the non-IABP group. Multivariable logistic regression analysis did not reveal a significant difference in 30-day survival (OR 1.37, 95% CI 0.91–2.07, p = 0.13). In the subgroup analysis, 30-day survival among patients without percutaneous coronary intervention (PCI) and stenosis of multiple coronary vessels were associated with IABP use. IABP use in patients with OHCA with ACS who received ECPR is not associated with 30-day survival. The use of IABP in patients who did not have PCI and have multiple coronary vessel stenoses warrants further study. [ABSTRACT FROM AUTHOR]

Image processing and computer vision on mobile devices have a wide range of applications such as digital image enhancement and augmented reality. While images acquired by cameras on mobile devices can be processed with generic image processing algorithms, there are numerous constraints and external issues that call for customized algorithms for such devices. In this paper, we survey mobile image processing and computer vision applications while highlighting these constraints and explaining how the algorithms have been modified/adapted to meet accuracy and performance demands. We hope that this paper will be a useful resource for researchers who intend to apply image processing and computer vision algorithms to real-world scenarios and applications that involve mobile devices. [ABSTRACT FROM AUTHOR]

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic–ischemic encephalopathy is a notable cause of neonatal death and developmental disabilities. To achieve better outcomes, it is important in treatment strategy selection to categorize the degree of hypoxia ischemia and evaluate dose response. In an asphyxia piglet model with histopathological brain injuries that we previously developed, animals survived 5 days after insult and showed changes in cerebral blood volume (CBV) that reflected the severity of injuries. However, little is known about the relationship between changes in CBV during and after insult. In this study, an HI event was induced by varying the amount and timing of inspired oxygen in 20 anesthetized piglets. CBV was measured using near-infrared time-resolved spectroscopy before, during, and 6 h after insult. Change in CBV was calculated as the difference between the peak CBV value during insult and the value at the end of insult. The decrease in CBV during insult was found to correlate with the increase in CBV within 6 h after insult. Heart rate exhibited a similar tendency to CBV, but blood pressure did not. Because the decrement in CBV was larger in severe HI, the CBV increment immediately after insult is considered useful for assessing degree of HI insult. [ABSTRACT FROM AUTHOR]

Background: Physical restraint has been commonly indicated to patients with brain dysfunction in neurocritical care. The effect of physical restraints on outcomes of critically ill adults remains controversial as no randomized controlled trials have compared its safety and efficacy, and the association between physical restraint requirement and neurological outcome in patients with subarachnoid hemorrhage (SAH) has not been fully examined. The aim of this study was to examine the association between physical restraint requirement and neurological outcomes in patients with SAH. Methods: A single-center, retrospective study was conducted on patients with acute phase SAH treated for > 72 h in the intensive care unit from 2014 to 2020. Patients were divided into three groups based on the amount of time required for physical restraint during the first 24–72 h after admission: no, intermittent, and continuous use of physical restraint. Unfavorable neurologic outcome, assessed using the modified Rankin scale upon hospital discharge, has been considered as primary end point. Results: Overall, 101 patients were included in the study, with 52 patients (51.5%) having unfavorable neurological outcomes. Among them, 46 patients (45.5%) did not use physical restraint, and 55 (54.5%) patients used physical restraint during the first 24–72 h after admission: 26 (25.7%) intermittent and 29 (28.7%) continuous. Multivariable logistic regression analysis showed that continuous use of physical restraint during the first 24–72 h after admission was significantly associated with unfavorable neurological outcomes in patients with SAH (odds ratio, 3.54; 95% confidence interval, 1.05–13.06; p = 0.042) compared with no physical restraint. Conclusions: Continuous use of physical restraint during the first 24–72 h after admission was more significantly associated with unfavorable neurological outcomes than no physical restraint among patients with SAH during the acute phase. [ABSTRACT FROM AUTHOR]

What is known and objective: Our objective is to report on a case of posterior reversible encephalopathy syndrome associated with pazopanib. Case description: A 64‐year‐old patient with uterine sarcoma developed PRES 3 days after pazopanib was initiated. After the discontinuation of pazopanib, the symptoms of PRES improved. What is new and Conclusion: The first report worldwide to describe a patient with uterine sarcoma experiencing PRES caused by pazopanib. Patients with uterine sarcoma may experience PRES, even in the early phase of pazopanib therapy. [ABSTRACT FROM AUTHOR]

In patients postcardiac arrest, it has been reported that the small value of the difference between mixed venous oxygen saturation (Sv o 2) and jugular venous oxygen saturation (Sjv o 2) is associated with poor neurologic outcome. However, the importance of the difference between mixed venous oxygen saturation and jugular venous oxygen saturation (ΔS o 2 [v − jv]) remains unknown in severe traumatic brain injury (TBI). The aim of this study was to examine whether ΔS o 2 (v − jv) is associated with neurologic outcome and mortality in patients with severe TBI. We conducted post hoc analyses of the Brain Hypothermia Study, a multicenter randomized controlled trial of mild therapeutic hypothermia for the treatment of severe TBI. The value of ΔS o 2 (v − jv) on day 1 and day 3 was compared between survivors (n = 65) and nonsurvivors (n = 25) or between patients with favorable (n = 47) and unfavorable (n = 43) neurologic outcomes. The reduction in ΔS o 2 (v − jv) on day 3 was −2.0% (range, −6.9% to 6.5%) in the nonsurvivor group and 6.3% (range, −2.5% to 16.7%) in the survivor group. The difference was statistically significant (P = 0.03). The same tendencies were observed in the nonsurvivor group on day 1 and in the unfavorable neurologic outcome group on day 1 and day 3, but the difference was not significant. The reduction in ΔS o 2 (v − jv) on day 3 was associated with high mortality in patients with severe TBI. [ABSTRACT FROM AUTHOR]

Background/objective: Simplified continuous electroencephalogram (cEEG) monitoring has shown improvement in detecting seizures; however, it is insufficient in detecting abnormal EEG patterns, such as periodic discharges (PDs), rhythmic delta activity (RDA), spikes and waves (SW), and continuous slow wave (CS), as well as nonconvulsive status epilepticus (NCSE). Headset-type continuous video EEG monitoring (HS-cv EEG monitoring; AE-120A EEG Headset™, Nihon Kohden, Tokyo, Japan) is a recently developed easy-to-use technology with eight channels. However, its ability to detect abnormal EEG patterns with raw EEG data has not been comprehensively evaluated. We aimed to examine the diagnostic accuracy of HS-cv EEG monitoring in detecting abnormal EEG patterns and NCSE in patients with altered mental status (AMS) with unknown etiology. We also evaluated the time required to initiate HS-cv EEG monitoring in these patients.Methods: We prospectively observed and retrospectively examined patients who were admitted with AMS between January and December 2017 at the neurointensive care unit at Asakadai Central General Hospital, Saitama, Japan. We excluded patients whose data were missing for various reasons, such as difficulties in recording, and those whose consciousness had recovered between HS-cv EEG and conventional cEEG (C-cEEG) monitoring. For the included patients, we performed HS-cv EEG monitoring followed by C-cEEG monitoring. Definitive diagnosis was confirmed by C-cEEG monitoring with the international 10-20 system. As the primary outcome, we verified the sensitivity and specificity of HS-cv EEG monitoring in detecting abnormal EEG patterns including PDs, RDA, SW, and CS, in detecting the presence of PDs, and in detecting NCSE. As the secondary outcome, we calculated the time to initiate HS-cv EEG monitoring after making the decision.Results: Fifty patients (76.9%) were included in the final analyses. The median age was 72 years, and 66% of the patients were male. The sensitivity and specificity of HS-cv EEG monitoring for detecting abnormal EEG patterns were 0.974 (0.865-0.999) and 0.909 (0.587-0.998), respectively, and for detecting PDs were 0.824 (0.566-0.926) and 0.970 (0.842-0.999), respectively. We diagnosed 13 (26%) patients with NCSE using HS-cv EEG monitoring and could detect NCSE with a sensitivity and specificity of 0.706 (0.440-0.897) and 0.970 (0.842-0.999), respectively. The median time needed to initiate HS-cv EEG was 57 min (5-142).Conclusions: HS-cv EEG monitoring is highly reliable in detecting abnormal EEG patterns, with moderate reliability for PDs and NCSE, and rapidly initiates cEEG monitoring in patients with AMS with unknown etiology. [ABSTRACT FROM AUTHOR]

Aim: The European Resuscitation Council guidelines recommend a slow rate of rewarming of 0.25 °C/h-0.5 °C/h for out-of-hospital cardiac arrest (OHCA) patients receiving therapeutic hypothermia (TH). Conversely, a very slow rewarming of 1 °C/day is generally applied in Japan. The rewarming duration ranged from less than 24 h up to more than 50 h. No randomized control trials have examined the optimal rewarming speed for TH in OHCA patients. Therefore, we examined the association between the rewarming duration and neurological outcomes in OHCA patients who received TH.Methods: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry, a multicenter prospective cohort study. Patients suffering from OHCA who received TH (target temperature, 34 °C) after the return of spontaneous circulation from 2005 to 2011 in 14 hospitals throughout Japan were enrolled. The rewarming duration was defined as the time from the beginning of rewarming at a target temperature of 34 °C until reaching 36 °C. The primary outcome was an unfavorable neurological outcome at hospital discharge, i.e., a cerebral performance category of 3-5.Results: The J-PULSE-HYPO study enrolled 452 OHCA patients. Of these, 328 were analyzed; 79.9% survived to hospital discharge, of which 56.4% had a favorable neurological outcome. Multivariable logistic regression analysis revealed that the rewarming duration was independently associated with unfavorable neurological outcomes [odds ratio (per 5 h), 0.89; 95% confidence interval, 0.79-0.99; p =  0.032].Conclusion: A longer rewarming duration was significantly associated with and was an independent predictor of favorable neurological outcomes in OHCA patients who received TH. [ABSTRACT FROM AUTHOR]

• Accurate cannulation is essential for extracorporeal cardiopulmonary resuscitation. • Japanese multicenter data were analyzed with propensity score matching. • Real-time ultrasound-guided cannulation was associated with shorter cannulation time. Extracorporeal cardiopulmonary resuscitation (ECPR), a bridge to treatments for cardiac arrest patients, can be technically challenging and requires expertise. While ultrasound guidance is frequently used for vascular access, its effects on cannulation time in patients treated with ECPR are poorly defined. We hypothesized that real-time ultrasound guidance would contribute to faster and safer cannulation for ECPR. This nationwide, multicenter, retrospective study analyzed data from 36 Japanese institutions. Patients who were over age 18 years and underwent ECPR between January 1, 2013, and December 31, 2018, were included. Patients who underwent open surgical vascular access were excluded. Cannulation time and outcomes of patients who underwent real-time ultrasound-guided cannulation (i.e., ultrasound-guided group) were compared to those cannulated without the use of real-time ultrasound guidance (control group) using propensity score matching analysis. The ultrasound-guided group comprised 510 cases, whereas the control group comprised 941 cases. Of those, 443 propensity score-matched pairs were evaluated. Cannulation time in the ultrasound-guided group was 2.5 minutes shorter than in the control group [difference, −2.5 minutes; 95% Confidence interval (CI), −3.7 to −1.3, p < 0.001]. The incidence of catheter-related complications and the incidence of the poor neurological outcomes (Cerebral Performance Category ≥3) did not differ between groups [Odds ratio (OR), 1.51; 95% CI, 0.64–3.74; OR, 1.08; 95% CI, 0.83–1.59]. Real-time ultrasound-guided cannulation was associated with shorter cannulation time of ECPR. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of different reperfusion strategies on neurological outcomes in patients with pulmonary embolism who received venoarterial extracorporeal membrane oxygenation (VA-ECMO) for out-of-hospital cardiac arrest (OHCA). This was a post-hoc analysis of a multicenter retrospective cohort study conducted in 36 institutions in Japan over six years. We included patients who underwent VA-ECMO and were diagnosed with pulmonary embolism caused by OHCA. Neurological outcomes were evaluated on the basis of the cerebral performance category at hospital discharge. We also assessed the association between reperfusion strategies and successful separation from ECMO. Among the 78 included patients, approximately half were successfully weaned from ECMO. Hospital mortality and favorable neurological outcomes at hospital discharge were 60.3% and 17.9%, respectively. Thirty-one patients (39.7%) underwent reperfusion strategies after ECMO, including 13 who received systemic thrombolytic therapy and 18 who underwent mechanical reperfusion strategy. After adjusting for prespecified covariates using the competing risk model, reperfusion strategies increased ECMO separation rate (systemic thrombolytic therapy: subdistribution hazard ratio [sHR] 2.24, 95% confidence interval [CI] 1.21–4.17, P = 0.011; mechanical reperfusion strategy: sHR 1.70, 95% CI 0.86–3.41, P = 0.129) compared with anticoagulation therapy alone, whereas higher cardiac Sequential Organ Failure Assessment score decreased ECMO separation rate (sHR 0.81, 95% CI 0.67–0.97, P = 0.020). Favorable neurological outcomes were observed in less than 20% of patients with OHCA due to pulmonary embolism undergoing ECMO. Reperfusion strategies may be associated with shorter ECMO durations in these patients. https://center6.umin.ac.jp/cgi-open-bin/ctr%5fe/ctr%5fview.cgi?recptno =R000041577 (unique identifier: UMIN000036490). [ABSTRACT FROM AUTHOR]

Highlights • Neospora caninum GRA6 promotes macrophages and induces IL-12 production in mice. • NcGRA6 alone or encased in OML conferred protection against murine neosporosis. • Protective efficacy of NcGRA6 induced with cellular immunity and IFN-γ production. • Immunization with NcGRA6 alone generated specific IgG1 after second immunization. Abstract Vaccination has the potential to be the most cost-effective control measure for reducing the economic burden of neosporosis in cattle. In this study, the immune-stimulatory effect of recombinant Neospora caninum dense granule protein 6 (NcGRA6) was confirmed via its triggering of IL-12p40 production in murine macrophages. BALB/c mice were immunized with recombinant NcGRA6 fused with glutathione S -transferase (GST) protein with or without oligomannose-coated-liposomes (OMLs) as the potential adjuvant. Specific IgG1 antibody production was observed from 21 and 35 days after the first immunization in NcGRA6+GST- and NcGRA6+GST-OML-immunized mice, respectively. However, specific IgG2a was detected 1 week after the infection, and IgG2a levels of the NcGRA6+GST- group were higher than those of the NcGRA6+GST-OML-group. Moreover, spleen cell proliferation with concomitant interferon-gamma production was detected in mice immunized with NcGRA6+GST, indicating that a significant cellular immune response was induced. Mouse survival rates against N. caninum challenge infection were 91.7% for NcGRA6+GST and 83.3% for NcGRA6+GST-OML, which were significantly higher than those of control groups (GST-OML: 25%, phosphate-buffered saline: 16.7%). This indicates that naked NcGRA6+GST induced protective immunity. Thus, our findings highlight the immune-stimulating potential of NcGRA6 and the ability to induce protective immunity against N. caninum infection in mice. [ABSTRACT FROM AUTHOR]

Purpose: In patients with aneurysmal subarachnoid hemorrhage (SAH), increased glucose variability (GV) is associated with increased mortality and cerebral infarction; however, there are no reports demonstrating an association between GV and neurological outcome. This study investigated whether GV had an independent effect on neurological outcomes in patients with SAH in the intensive care unit. Materials and Methods: Consecutive adult patients hospitalized with SAH between January 1, 2009, and May 31, 2015 (N = 122) were retrospectively reviewed. Univariate/multivariate analyses were performed to identify independent predictors of poor neurological outcome. Patients were divided according to the mean glucose level (80-139 vs 140-200 mg/dL) and further subdivided using quartiles (Q) of the standard deviation (SD, representing variability) of the glucose level (Q1, Q2 + 3, and Q4). Results: Unfavorable neurological outcomes occurred in 44.2% of the patients. On multiple regression analysis, age, Hunt and Kosnik grade, SD of glucose (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17; P < .01), and minimum blood glucose level (OR, 0.95; 95% CI, 0.91-0.99; P < .01) were significantly associated with unfavorable neurological outcomes. Both groups (mean glucose levels: 80-139 and 140-200 mg/dL groups) had increasing unfavorable neurological outcomes with increasing SD of glucose (Q1, 15.0%; Q2 + 3, 40.0%; Q4, 52.4% and Q1, 44.4%; Q2 + 3, 50%; Q4, 88.9% in the 80-139 and 140-200 mg/dL groups, respectively). Patients with minimum glucose of <90 mg/dL comprised >50% of unfavorable neurological outcome. Conclusion: Increased GV was an independent predictor of unfavorable neurological outcomes in patients with SAH. [ABSTRACT FROM AUTHOR]

Cases of Clostridium perfringen s septicemia, such as liver abscess, often develop a rapidly progressive intravascular hemolysis and coagulation; the mortality rate with current standard care including antibiotics and surgery is high. Herein, we firstly investigated the effects of gas gangrene antitoxin (GGA) (antitoxin against C. perfringens ) and recombinant human soluble thrombomodulin (rTM) on the hemolysis, coagulation status, inflammatory process, and mortality in α-toxin-treated rats. Male 11-week-old Sprague Dawley rats were randomly divided into five groups: control group, α-toxin group, GGA group, rTM group, and combined GGA and rTM (combination group). After α-toxin injection, mortality and platelet counts, and hemolysis were observed for 6 h. The fibrin/fibrinogen degradation products (FDP), and plasma high-mobility group box 1 (HMGB1) were also measured at 6 h. The combination group demonstrated 100% survival compared with 50% survival in the α-toxin group and demonstrated significantly improved hemolysis, platelet counts, and lactate levels compared with those in the α-toxin group (p < .01). The FDP and HMGB1 levels in the combination therapy group were significantly lower than those in the α-toxin group (p < .05). Combination therapy with GGA and rTM administration is applicable as adjunct therapy for fatal C. perfringens sepsis. [ABSTRACT FROM AUTHOR]

This study aimed to describe the characteristics of cases of out-of-hospital cardiac arrest (OHCA) with an initial asystole rhythm in which extracorporeal cardiopulmonary resuscitation (ECPR) was introduced and discuss the clinical indications for ECPR in such patients. This was a secondary analysis of the SAVE-J II study, a retrospective, multicentre, registry study involving 36 participating institutions in Japan. Patients with an initial asystole rhythm were selected. Favourable neurological outcomes (cerebral performance categories 1–2) constituted the primary outcome. In total, 202 patients met the inclusion criteria, with favourable neurological outcomes at hospital discharge in 12 patients (5.9%). Causes of cardiac arrest with favourable neurological outcomes were hypothermia (7 cases), acute coronary syndrome (2 cases), arrhythmia (2 cases), and pulmonary embolism (1 case). Among patients with non-hypothermia (temperature ≥32 °C) on hospital arrival with the cardiac rhythm of asystole or pulseless electrical activity (PEA) on arrival, all 107 patients (66 asystole, 41 PEA) who lacked one or more of the requirements (witness; bystander CPR; signs of life or pupil < 5 mm) had unfavourable neurological outcomes. All 5 cases with favourable neurological outcomes, except for 1 case with a short duration of no-flow time that was highly suspected based on the patient's history, met all the requirements on hospital arrival. A total of 202 ECPR cases with an initial asystole rhythm, including 12 patients with favourable neurological outcomes, were described. Even if the initial cardiac rhythm is asystole, ECPR could be considered if certain conditions are met. [ABSTRACT FROM AUTHOR]

The effects of hyperoxia on the neurological outcomes of patients with severe traumatic brain injury (TBI) are still controversial. We examined whether the partial pressure of arterial oxygen (PaO2) and hyperoxia were associated with neurological outcomes and survival by conducting post-hoc analyses of the Brain Hypothermia (B-HYPO) study, a multi-center randomized controlled trial of mild therapeutic hypothermia for severe TBI. The differences in PaO2 and PaO2/fraction of inspiratory oxygen (P/F) ratio on the 1st day of admission were compared between patients with favorable ( n = 64) and unfavorable ( n = 65) neurological outcomes and between survivors ( n = 90) and deceased patients ( n = 39). PaO2 and the P/F ratio were significantly greater in patients with favorable outcomes than in patients with unfavorable neurological outcomes (PaO2: 252 ± 122 vs. 202 ± 87 mm Hg, respectively, p = 0.008; P/F ratio: 455 ± 171 vs. 389 ± 155, respectively, p = 0.022) and in survivors than in deceased patients (PaO2: 242 ± 117 vs. 193 ± 75 mm Hg, respectively, p = 0.005; P/F ratio: 445 ± 171 vs. 370 ± 141, respectively, p = 0.018). Similar tendencies were observed in subgroup analyses in patients with fever control and therapeutic hypothermia, and in patients with an evacuated mass or other lesions (unevacuated lesions). PaO2 was independently associated with survival (odds ratio 1.008, p = 0.037). These results suggested that early-stage hyperoxia might be associated with favorable neurological outcomes and survival following severe TBI. [ABSTRACT FROM AUTHOR]

We investigated associations between blood glucose levels and clinical outcomes in participants of the multi-center randomized controlled Brain-Hypothermia (B-HYPO) study. Patients with severe traumatic brain injury (TBI, Glasgow Coma Scale 4-8) were assigned to therapeutic hypothermia (TH, 32-34°C, n = 98) or fever control (35.5-37.0°C, n = 50) groups. TH patients were cooled as soon as possible for ≥72 h and rewarmed at a rate of <1°C/d. We recorded blood glucose (BG) levels on days 0, 1, and 3 after treatment initiation, and day 1 after rewarming. The Glasgow Outcome Scale was assessed at 6 months. Median BG levels decreased from day 0 to day 1 (163 vs. 132 mg/dL, p = 0.0062) in the fever control group. In contrast, a decrease was observed from day 1 to day 3 (157.5 vs. 126 mg/dL, p < 0.001) in the TH group. Day 1 BG was higher in the TH group compared with the fever control group ( p = 0.0252). At day 0, BG levels were higher in non-survivors compared with survivors across all patients ( p = 0.0035), the TH group ( p = 0.0125), and the non-surgical group ( p = 0.0236). Higher day 1 BG levels were observed in non-survivors compared with survivors across all patients ( p = 0.0071), the fever control group ( p = 0.0495), and the surgical group ( p = 0.0364). In the TH group, the initial stress hyperglycemia was sustained the next day after TH induction. Day 1 BG predicted outcome in TBI patients with TH and fever control. Our findings indicate the significance of BG control particularly during TH treatment. [ABSTRACT FROM AUTHOR]

Aim: Out-of-hospital cardiac arrest (OHCA) is associated with poor prognosis. Cerebral microdialysis (CMD) is an efficient sampling technique to detect neurochemical changes in brain interstitial tissue. In this retrospective study, we hypothesised that there are different CMD levels between patients with favourable and unfavourable neurological outcomes.Methods: Data of patients with OHCA admitted to Kagawa University Hospital and administered therapeutic hypothermia (TH) were collected. Using a CMD probe, extracellular glucose, lactate and pyruvate levels were measured hourly along with intracranial perfusion pressure (ICP) and cerebral perfusion pressure (CPP) for the initial 72h during TH. The lactate/pyruvate (LP) ratio was calculated. Patients were divided into favourable [Glasgow-Pittsburgh cerebral performance category 1-2 at 30days after cardiac arrest] or unfavourable neurological outcome groups. CMD biochemical markers and blood lactate and glucose levels were compared between two groups.Results: Ten patients were included. ICP was significantly higher in the unfavourable than in the favourable neurological outcome group; there were no significant differences with respect to CPP. The CMD LP ratio in the unfavourable outcome group progressively increased; significant differences were observed on days 2, 3 and 4 (p<0.01). Significant differences in blood lactate levels were observed between the groups only on day 3.5. CMD and blood glucose levels were higher in the unfavourable than in the favourable outcome group during TH.Conclusion: The association of CMD levels with long-term outcomes would be better defined in a large randomised prospective study. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that administration of oligomannose-coated liposomes (OMLs), in which an antigen is encased, induce antigen-specific Th1 immune responses and CTLs. In the present study, we showed that TLR4 signaling is required for the induction of specific immune responses following OML administration. In C3H/HeJ mice, which express a dysfunctional TLR4, the antigen-specific Th1 immune response could not be elicited following intraperitoneal administration of OVA-encased OMLs (OML/OVA). However, OML uptake by peritoneal cells, the subsequent production of IL-12 and the upregulation of co-stimulatory molecules and MHC class II on the cells in response to OML uptake occurred in C3H/HeJ mice to the same extent as in wild type C3H/HeN mice. In addition, peritoneal phagocytic cells from TLR4 −/− mice that ingest OML/OVA can activate CD4 + T cells from OT-II mice. On the other hand, the number of OML-ingesting peritoneal cells that migrated into mesenteric lymph nodes in C3H/HeJ mice was significantly less than that in C3H/HeN mice. Therefore, the chemotactic capability of OML-ingesting peritoneal phagocytes to the draining lymph nodes rather than the activation and maturation of the cells in response to OML uptake is impaired by lack of TLR4 signaling, and disorder of the Th1 immune response elicited by OMLs in mice, which lack TLR4 signaling, is due to the impairment of cell migration following OML uptake. [ABSTRACT FROM AUTHOR]

Background Several studies using trauma data banks and registers showed that age, Glasgow Coma Scale (GCS), Injury Severity Score, and intraventricular hemorrhage were independent factors for neurologic outcomes in geriatric patients with traumatic brain injury (TBI). However, these analyses did not comprehensively evaluate factors particularly associated with geriatric patients. We aimed to identify factors particularly associated with geriatric patients that affect neurologic outcomes in TBI. Methods Patients aged ≥65 years who were hospitalized consecutively in Kagawa University Hospital with severe TBI between 1 January 2008 and 31 October 2015 were retrospectively reviewed. We evaluated background factors particularly associated with geriatric patients, including comorbidities (Charlson Comorbidity Index [CCI]), nutritional status (serum albumin level), and presence/absence of antiplatelet and anticoagulant drugs, in addition to baseline characteristics. Multivariate analyses were performed to identify independent predictors of unfavorable neurologic outcomes (UO), as defined as a Glasgow Outcome Scale score of 1–3 at discharge from hospital. The association between CCI and UO was evaluated in a subgroup analysis. Results UO occurred in 65.0% of 140 patients. Multivariate analyses showed that the CCI (odds ratio, 1.91; 95% confidence interval, 1.21–3.29; P = 0.011), age, and GCS were independent predictors of UO. In subgroup analyses of patients with an initial GCS score of 13–15, the rate of UO significantly increased with CCI score (CCI 0, 35.5%; CCI 1 or 2, 39.4%; CCI >2, 83.3%; P < 0.01). Conclusions CCI was an independent predictor of UO in geriatric patients with severe TBI. [ABSTRACT FROM AUTHOR]

Yacon ( Smallanthus sonchifolius), a native Andean plant, has been cultivated as a crop and locally used as a traditional folk medicine for the people suffering from diabetes and digestive/renal disorders. However, the medicinal properties of this plant and its processed foods have not been completely established. This study investigates the potent antioxidative effects of herbal tea leaves from yacon in different free radical models and a ferric reducing model. A hot-water extract exhibited the highest yield of total polyphenol and scavenging effect on 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical among four extracts prepared with hot water, methanol, ethanol, and ethylacetate. In addition, a higher reducing power of the hot-water extract was similarly demonstrated among these extracts. Varying concentrations of the hot-water extract resulted in different scavenging activities in four synthetic free radical models: DPPH radical (EC50 28.1 μg/mL), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical (EC50 23.7 μg/mL), galvinoxyl radical (EC50 3.06 μg/mL), and chlorpromazine cation radical (EC50 475 μg/mL). The yacon tea-leaf extract further demonstrated superoxide anion (O2−) radical scavenging effects in the phenazine methosulfate-NADH-nitroblue tetrazolium (EC50 64.5 μg/mL) and xanthine oxidase assay systems (EC50 20.7 μg/mL). Subsequently, incubating human neutrophilic cells in the presence of the tea-leaf extract could suppress the cellular O2− radical generation (IC50 65.7 μg/mL) in a phorbol 12-myristate 13-acetate-activated cell model. These results support yacon tea leaves may be a good source of natural antioxidants for preventing O2− radical-mediated disorders. [ABSTRACT FROM AUTHOR]

B Conclusions: b The current ECPR data including 1,463 OHCA patients showed 13.3% of favorable neurological outcomes at hospital discharge in unselected OHCA patients. This study aimed to assess patient characteristics, outcomes, and complications of ECPR practice in patients with OHCA. B Introduction: b Several observational extracorporeal cardiopulmonary resuscitation (ECPR) studies with clinical data have been published; however, those studies have the great limitations with relatively small numbers, and the real-world data of ECPR in out-of-hospital cardiac arrest (OHCA) patients is lacking. [Extracted from the article]