Yasutaka Koga

Hyperglycemia enhances excessive superoxide anion radical generation, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats

The aim of this study was to confirm the effect of acute hyperglycemia on the superoxide anion radical (O(2)(-)) generation, using a novel electrochemical O(2)(-) sensor in forebrain ischemia/reperfusion rats. Fourteen male Wistar rats were allocated to a normoglycemia group (n= 7) and a hyperglycemia group (n=7). Hyperglycemia was induced by intravenous infusion of glucose solution. Forebrain ischemia was induced by bilateral common carotid arteries occlusion with hemorrhagic hypotension for 10 min and then was reperfused. The generated O(2)(-) was measured as the current produced, which was integrated as a quantified partial value of electricity (Q), in the jugular vein using the O(2)(-) sensor. The reacted O(2)(-) current and the Q began to increase gradually during the forebrain ischemia in both groups. These values increased remarkably just after reperfusion in the normoglycemia group and were further increased significantly in the hyperglycemia group after the reperfusion. Concentrations of malondialdehyde (MDA) and high-mobility group box 1 (HMGB1) in the brain and plasma, and soluble intercellular adhesion molecule-1 (ICAM-1) in the plasma in the hyperglycemia group were significantly higher than those in the normoglycemia group. Brain and plasma MDA, HMGB1, and ICAM-1 were correlated with a sum of Q during ischemia and after reperfusion. In conclusion, acute transient hyperglycemia enhanced the O(2)(-) generation in blood and exacerbated oxidative stress, early inflammation, and endothelial injury after the forebrain ischemia/reperfusion in the rats.

Urinary trypsin inhibitor suppresses excessive superoxide anion radical generation in blood, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats.

Abstract Objectives: To investigate the effects of ulinastatin, a urinary trypsin inhibitor (UTI), on jugular venous superoxide radical (O−2·) generation, oxidative stress, early inflammation, and endothelial activation in forebrain ischemia/reperfusion (FBI/R) rats.Methods: Fourteen Wistar rats were allocated to a control group (n = 7) and a UTI group (n = 7). Throughout the experiments, O−2· in the jugular vein was measured by the produced current using a novel electrochemical O−2· sensor. Forebrain ischemia was induced by occlusion of the bilateral common caroti darteries with hemorrhagic hypotension for 20 min, followed by reperfusion. In the UTI group, UTI (5 U/g) was administered intravenously immediately after reperfusion. At 60 min after reperfusion, plasma and brain were harvested, and malondialdehyde, high-mobility group box 1 (HMGB1) protein, and intercellular adhesion molecule-1 (ICAM-1) were measured. Results: O−2· current increased gradually during forebrain ischemia in both groups. The current increased markedly in the control group immediately after reperfusion but was significantly attenuated in the UTI group after reperfusion. Brain and plasma malondialdehyde, HMGB1, and ICAM-1 were significantly attenuated in the UTI group compared with those in the control group, except for brain HMGB1, which was associated with the amount of O−2· generated during FBI/R. Discussion: UTI suppressed jugular venous O−2· generation, oxidative stress, early inflammation, and endothelial activation in FBI/R rats. Therefore, UTI might be a useful agent for the therapy of the cerebral ischemia/reperfusion pathophysiology.

Long-lasting response to crizotinib in brain metastases due to EML4-ALK-rearranged non-small-cell lung cancer

Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib, an oral ATP-competitive selective inhibitor of ALK. However, crizotinib exhibits extremely poor blood–brain barrier penetration; therefore, it is considered to play a limited role in the treatment of brain metastases. We present a case of a 50-year-old man with a diagnosis of ALK-rearranged NSCLC with brain metastasis and malignant pleural effusion. Despite the several systemic chemotherapy regimens and whole brain radiotherapy, brain metastasis was refractory; therefore, crizotinib was initiated. A CT scan showed a slight reduction in the brain metastasis and no change in intrathoracic disease 17 weeks after initiating crizotinib. Moreover, CT obtained 12 months after crizotinib treatment revealed brain metastasis without progression. To our knowledge, the present case is the second report of crizotinib-responsive brain metastases due to echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)-rearranged NSCLC.

Effects of mechanical chest compression device with a load-distributing band on post-resuscitation injuries identified by post-mortem computed tomography.

OBJECTIVE To determine the effects of cardiopulmonary resuscitation (CPR) with AutoPulse™ (LDB-CPR) on post-resuscitation injuries identified by post-mortem computed tomography (PMCT). AutoPulse™ is a novel mechanical chest-compression device with a load-distributing band (LDB) that may affect post-resuscitation injury identified by PMCT. METHODS We conducted a retrospective cohort study of non-traumatic adult out-of-hospital cardiac arrest patients whose death was confirmed in our emergency department between October 2009 and September 2014. Patients were divided according to whether LDB-CPR (LDB-CPR group) or manual CPR only (manual CPR only group) was performed. The background characteristics and post-resuscitation injuries identified by PMCT were compared between both groups. Logistic regression was used to identify risk factors for posterior rib fracture and abdominal injury. RESULTS Overall, 323 patients were evaluated, with 241 (74.6%) in the LDB-CPR group. The total duration of CPR was significantly longer in the LDB-CPR group than in the manual CPR only group. Posterior rib fracture, hemoperitoneum, and retroperitoneal hemorrhage were significantly more frequent in the LDB-CPR group. The frequencies of anterior/lateral rib and sternum fracture were similar in both groups. Pneumothorax tended to be more frequent in the LDB-CPR group, although not significantly. LDB-CPR was an independent risk factor for posterior rib fracture (odds ratio 30.57, 95% confidence interval 4.15-225.49, P=0.001) and abdominal injury (odds ratio 4.93, 95% confidence interval 1.88-12.95, P=0.001). CONCLUSIONS LDB-CPR was associated with higher frequencies of posterior rib fracture and abdominal injury identified by PMCT. PMCT findings should be carefully examined after LDB-CPR.

Extent of pleural effusion on chest radiograph is associated with failure of high-flow nasal cannula oxygen therapy.

PURPOSE The purpose of the study was to determine whether pleural effusion (PE) is associated with a failure of high-flow nasal cannula (HFNC) therapy. MATERIALS AND METHODS We conducted a single-center retrospective study. Seventy-three patients with acute respiratory failure given HFNC therapy between January 2012 and December 2014 were reviewed. HFNC failure was defined as intubation or noninvasive positive pressure ventilation following HFNC therapy. The numbers of quadrants with consolidation or ground glass opacity were counted on chest radiographs performed within 24 hours before starting HFNC therapy, and the PE score was calculated. PE score was the original score, verified by the computed tomographic images of some of the study patients. RESULTS Overall, 29 of 73 experienced HFNC failure. PE score was significantly greater in the HFNC failure group, but the number of quadrants with opacity was not significantly different. Age and Sequential Organ Failure Assessment (SOFA) score were significantly greater in the HFNC failure group. The PE (odds ratio, 1.49; 95% confidence interval, 1.10-2.02; P = .01) and SOFA (odds ratio, 1.33; 95% confidence interval, 1.05-1.68; P = .02) scores were independently associated with HFNC failure in multivariate analysis. CONCLUSIONS The extent of PE on chest radiograph and SOFA score were associated with HFNC failure.

Early enteral nutrition is associated with reduced in-hospital mortality from sepsis in patients with sarcopenia

Purpose: To determine whether the association of early enteral nutrition (EEN) with mortality from sepsis differs between patients with and without sarcopenia. Materials and methods: We retrospectively reviewed septic patients treated at our centre between January 2010 and August 2017. The skeletal muscle area (SMA) at the level of the third lumbar vertebra was measured with CT on admission, and sarcopenia was defined as SMA < 80% of the predicted value. Patients were divided into two subgroups (sarcopenic and non‐sarcopenic patients), and in‐hospital mortality was compared in patients treated with and without EEN within each subgroup. We used logistic regression to examine factors associated with in‐hospital mortality in each subgroup. Results: EEN was administered to 35/91 sarcopenic patients and 43/100 non‐sarcopenic patients. In‐hospital mortality did not differ between non‐sarcopenic patients with EEN and those without EEN (16% vs 16%, P = 0.947), but was significantly lower in sarcopenic patients with EEN than in those without EEN (9% vs 34%, P = 0.005). Logistic regression showed that EEN was independently associated with reduced in‐hospital mortality in sarcopenic patients (OR 0.18, 95% CI 0.05–0.71, P = 0.014), but not in non‐sarcopenic patients. Conclusions: EEN may be more beneficial in sarcopenic patients. HighlightsEffects of early enteral nutrition (EEN) on mortality from sepsis remain uncertain.Effects of EEN may differ with patient characteristics.EEN was independently associated with reduced in‐hospital mortality in sarcopenia, but not in non‐sarcopenia.Sarcopenic patients may be a suitable sub‐group for EEN.

Splenic volume in severe sepsis is associated with disease severity and pneumococcal infection

A small spleen, which is occasionally found in patients with pneumococcal sepsis, may increase pneumococcal susceptibility because of splenic malfunction. However, a small spleen may also originate from severe disease. We carried out a retrospective study to evaluate the association between splenic volume and severe pneumococcal sepsis or disease severity.

Cardiac arrest due to massive hemorrhage from uterine adenomyosis with leiomyoma successfully treated with damage control resuscitation

A 57‐year‐old woman was transferred to our emergency department by ambulance with cardiopulmonary arrest caused by massive genital bleeding. Cardiopulmonary resuscitation, including massive transfusion, was carried out and the return of spontaneous circulation was achieved. A giant uterine tumor was considered the source of the bleeding. Although hysterectomy was necessary to achieve definitive hemostasis, the patient was unable to tolerate the operation because of hemodynamic instability, acidosis, and coagulopathy. Therefore, we undertook vaginal gauze packing and uterine artery embolization to attain temporary hemostasis, which resulted in hemodynamic stabilization. Abdominal hysterectomy for definitive hemostasis was carried out 10 h after the embolization.