Periprocedural bleeding was significantly associated with CI-AKI, with CI-AKI incidence correlating with bleeding severity.

ObjectiveThis study evaluated the manner in which coronary dominance affects in-hospital outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).BackgroundPrevious studies have shown that left dominant coronary anatomies are associated with worse prognoses in patients with coronary artery disease.MethodsData were analyzed from 4873 ACS patients undergoing PCI between September 2008 and April 2013 at 14 hospitals participating in the Japanese Cardiovascular Database Registry. The patients were grouped based on diagnostic coronary angiograms performed prior to PCI; those with right- or co-dominant anatomy (RD group) and those with left-dominant anatomy (LD group).ResultsThe average patient age was 67.6±11.8 years and both patient groups had similar ages, coronary risk factors, comorbidities, and prior histories. The numbers of patients presenting with symptoms of heart failure, cardiogenic shock, or cardiopulmonary arrest were significantly higher in the LD group than in the RD group (heart failure: 650 RD patients [14.7%] vs. 87 LD patients [18.8%], P = 0.025; cardiogenic shock: 322 RD patients [7.3%] vs. 48 LD patients [10.3%], P = 0.021; and cardiopulmonary arrest: 197 RD patients [4.5%] vs. 36 LD patients [7.8%], P = 0.003). In-hospital mortality was significantly higher among LD patients than among RD patients (182 RD patients [4.1%] vs. 36 LD patients [7.8%], P = 0.001). Multivariate logistic regression analysis revealed that LD anatomy was an independent predictor for in-hospital mortality (odds ratio, 1.75; 95% confidence interval, 1.06–2.89; P = 0.030).ConclusionAmong ACS patients who underwent PCI, LD patients had significantly worse in-hospital outcomes compared with RD patients, and LD anatomy was an independent predictor of in-hospital mortality.

T cells must migrate to encounter antigen-presenting cells and perform their roles in host defense. Here, we found that autocrine stimulation of the purinergic receptor P2Y11 regulates the migration of human CD4 T cells. P2Y11 receptors redistributed from the front to the back of polarized cells where they triggered intracellular cAMP/PKA signals that attenuated mitochondrial metabolism at the back. The absence of P2Y11 receptors at the front of cells resulted in hotspots of mitochondrial metabolism and localized ATP production that stimulated P2X4 receptors, Ca2+ influx, and pseudopod protrusion at the front. This regulatory function of P2Y11 receptors depended on their subcellular redistribution and autocrine stimulation by cellular ATP release and was perturbed by indiscriminate global stimulation. We conclude that excessive extracellular ATP—such as in response to inflammation, sepsis, and cancer—disrupts this autocrine feedback mechanism, which results in defective T cell migration, impaired T cell function, and loss of host immune defense.

Geriatric trauma is a major socio-economic problem, especially among the aging Japanese society. Geriatric people are more vulnerable to trauma than younger people; thus, their outcomes are often severe. This study evaluates the characteristics of geriatric trauma divided by age in the Japanese population. We evaluated trauma characteristics in patients (n = 131,088) aged ≥ 65 years by segregating them into 2 age-based cohorts: age 65–79 years (65–79 age group; n = 70,707) and age ≥ 80 years (≥ 80 age group; n = 60,381). Clinical characteristics such as patient background, injury mechanism, injury site and severity, treatment, and outcome were examined. Injuries among men were more frequent in the 65–79 age group (58.6%) than in the ≥ 80 age group (36.3%). Falls were the leading cause of trauma among the 65–79 age group (56.7%) and the ≥ 80 age group (78.9%). In-hospital mortality was 7.7% in the 65–79 age group and 6.6% in the ≥ 80 age group. High fall in the ≥ 80 age group showed 30.5% mortality. The overall in-hospital mortality was 11.8% (the 65–79 age group, 12.3%; the ≥ 80 age group, 11.2%). Most hospitalized patients were transferred to another hospital (the 65–79 age group, 52.5%; the ≥ 80 age group, 66.2%). We demonstrated the epidemiological characteristics of Japanese geriatric trauma patients. The overall in-hospital mortality was 11.8%, and fall injury in the ≥ 80 age group required caution of trauma care.

Aim: Early outcome prediction for out-of-hospital cardiac arrest with initial shockable rhythm is useful in selecting the choice of resuscitative treatment by clinicians. This study aimed to develop and validate a machine learning-based outcome prediction model for out-of-hospital cardiac arrest with initial shockable rhythm, which can be used on patient's arrival at the hospital. Methods: Data were obtained from a nationwide out-of-hospital cardiac arrest registry in Japan. Of 43,350 out-of-hospital cardiac arrest patients with initial shockable rhythm registered between 2013 and 2017, patients aged <18 years and those with cardiac arrest caused by external factors were excluded. Subjects were classified into training (n = 23,668, 2013-2016 data) and test (n = 6381, data from 2017) sets for validation. Only 19 prehospital variables were used for the outcome prediction. The primary outcome was death at 1 month or survival with poor neurological function (cerebral performance category 3-5; "poor" outcome). Several machine learning models, including those based on logistic regression, support vector machine, random forest, and multilayer perceptron classifiers were compared. Results: In validation analyses, all machine learning models performed satisfactorily with area under the receiver operating characteristic curve values of 0.882 [95% confidence interval [CI]: 0.869-0.894] for logistic regression, 0.866 [95% CI: 0.853-0.879] for support vector machine, 0.877 [95% CI: 0.865-0.890] for random forest, and 0.888 [95% CI: 0.876-0.900] for multilayer perceptron classifiers. Conclusions: A favourable machine learning-based prognostic model available to use on patient arrival at the hospital was developed for out-ofhospital cardiac arrest with initial shockable rhythm.

Objective: Monocytes and macrophages produce interleukin-1β (IL-1β) by inflammasome activation which involves ATP release, pannexin-1 (panx1) channels, and P2X7 receptors. However, IL-1β can also be produced in an inflammasome-independent fashion. Here we studied if this mechanism also involves ATP signaling and how it contributes to inflammasome activation. Design: In vitro studies with human cells and randomized animal experiments. Setting: Preclinical academic research laboratory. Subjects: Wild-type (WT) C57BL/6 and panx1 knockout (KO) mice, healthy human subjects for cell isolation. Interventions: Human monocytes and U937 macrophages were treated with different inhibitors to study how purinergic signaling contributes to toll-like receptor (TLR) induced cell activation and IL-1β production. WT and panx1 KO mice were subjected to cecal ligation and puncture (CLP) to study the role of purinergic signaling in IL-1β production and host immune defense. Measurements and main results: TLR agonists triggered mitochondrial ATP production and ATP release within seconds. Inhibition of mitochondria, ATP release, or P2 receptors blocked p38 MAPK and caspase-1 activation and IL-1β secretion. Mice lacking panx1 failed to activate monocytes, to produce IL-1β, and to effectively clear bacteria following CLP. Conclusions: Purinergic signaling has two separate roles in monocyte/macrophage activation, namely to facilitate the initial detection of danger signals via TLRs and subsequently to regulate NLRP3 inflammasome activation. Further dissection of these mechanisms may reveal novel therapeutic targets for immunomodulation in critical care patients.

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Sivelestat sodium, a selective neutrophil elastase inhibitor, is the only commercially available, specific therapy for acute respiratory distress syndrome (ARDS); however, its clinical efficacy is controversial. We aimed to evaluate appropriate indications for its use in ARDS. Methods: We studied 66 patients with ARDS who were treated with sivelestat sodium. They were divided into survivors (n = 37) or non-survivors (n = 29) at 60 days, and clinical characteristics were analyzed. Results: Patients' backgrounds evaluated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the sequential organ failure assessment (SOFA) score were significantly different between both groups (survivors versus non-survivors: APACHE II score, 14.7 AE 6.7 versus 20.5 AE 4.7, P < 0.01; SOFA, 7.25 AE 2.5 versus 9.82 AE 3.5, P < 0.01). There were no significant differences in other patients' characteristics. On receiver operator characteristic analysis of APACHE II scores before the use of sivelestat sodium, the estimated cutoff value for survival was calculated to be 18.5. On receiver operator characteristic analysis of the PaO 2 /FIO 2 ratio, the area under the curve was the highest 3 days after the treatment, with the optimal cutoff point at 198. Conclusion: An APACHE II score ≤18, and a PaO 2 /FIO 2 ratio >198 at 3 days after the use of sivelestat sodium predicted a good outcome.