Yasuhiro Kuroda

Plasma brain natriuretic peptide as a surrogate marker for cardioembolic stroke

BackgroundCardioembolic stroke generally results in more severe disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic stroke from non-cardioembolic stroke (atherothrombotic stroke and lacunar stroke). In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic stroke or non-cardioembolic stroke, and assessed the prediction factors of plasma brain natriuretic peptide and whether we could differentiate between stroke subtypes on the basis of plasma brain natriuretic peptide concentrations in addition to patients clinical variables.MethodsOur patient cohort consisted of 131 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005 to December 31, 2007. The mean age of patients (43 females, 88 males) was 69.6 ± 10.1 years. Sixty-two patients had cardioembolic stroke; the remaining 69 patients had non-cardioembolic stroke (including atherothrombotic stroke, lacunar stroke, or the other). Clinical variables and the plasma brain natriuretic peptide were evaluated in all patients.ResultsPlasma brain natriuretic peptide was linearly associated with atrial fibrillation, heart failure, chronic renal failure, and left atrial diameter, independently (F4,126 = 27.6, p < 0.0001; adjusted R2 = 0.45). Furthermore, atrial fibrillation, mitral regurgitation, plasma brain natriuretic peptide (> 77 pg/ml), and left atrial diameter (> 36 mm) were statistically significant independent predictors of cardioembolic stroke in the multivariable setting (Χ2 = 127.5, p < 0.001).ConclusionIt was suggested that cardioembolic stroke was strongly predicted with atrial fibrillation and plasma brain natriuretic peptide. Plasma brain natriuretic peptide can be a surrogate marker for cardioembolic stroke.

Effectiveness of lower target temperature therapeutic hypothermia in post-cardiac arrest syndrome patients with a resuscitation interval of ≤30 min.

BackgroundTherapeutic hypothermia (TH) is a standard strategy to reduce brain damage in post-cardiac arrest syndrome (PCAS) patients. However, it is unknown whether the target temperature should be adjusted for PCAS patients in different states.MethodsParticipants in the J-PULSE-Hypo study database were divided into lower (32.0–33.5xa0°C; Group L) or moderate (34.0–35.0xa0°C; Group M) temperature groups. Primary outcome was a favourable neurological outcome (proportion of patients with a Glasgow-Pittsburgh Cerebral Performance Category [CPC] of 1–2 on day 30). We compared between the two groups and in subgroups of patients divided by age and resuscitation interval (interval from collapse to return of spontaneous circulation) by propensity score (PS) analysis.ResultsOverall, 467 participants were analysed. The proportions of patients with favourable neurological outcomes were as follows (Group L vs. Group M) (OR; Odds ratio): all patients, 64xa0% (nu2009=u200942) vs. 55xa0% ((nu2009=u2009424) (PS; OR 1.381 (0.596–3.197)), Pu2009=u20090.452) and resuscitation intervalu2009≤u200930xa0min, 88xa0% (nu2009=u200924) vs. 64xa0% ((nu2009=u2009281) (PS; OR 7.438 (1.769–31.272)), Pu2009=u20090.007).ConclusionsPCAS patients with a resuscitation interval of <30xa0min may be candidates for TH with a target temperature of <34xa0°C.Trial registrationUniversity Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000001935; available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000002348&language=J.

Probing the molecular mechanisms of neuronal degeneration: importance of mitochondrial dysfunction and calcineurin activation

Cerebral injury is a critical aspect of the management of patients in intensive care. Pathological conditions induced by cerebral ischemia, hypoxia, head trauma, and seizure activity can result in marked residual impairment of cerebral function. We have investigated the potential mechanisms leading to neuronal cell death in pathological conditions, with the aim of discovering therapeutic targets and methods to minimize neuronal damage resulting from insults directed at the central nervous system (CNS). Over the years, deeper understanding of the mechanisms of neuronal cell death has indeed evolved, enabling clinical critical care management to salvage neurons that are at the brink of degeneration and to support recovery of brain function. However, no substantial breakthrough has been achieved in the quest to develop effective pharmacological neuroprotective therapy directed at tissues of the CNS. The current situation is unacceptable, and preservation of function and protection of the brain from terminal impairment will be a vital medical issue in the twenty-first century. To achieve this goal, it is critical to clarify the key mechanisms leading to neuronal cell death. Here, we discuss the importance of the calcineurin/immunophilin signal transduction pathway and mitochondrial involvement in the detrimental chain of events leading to neuronal degeneration.

Venomous snake bites: clinical diagnosis and treatment

Snake bites are life-threatening injuries that can require intensive care. The diagnosis and treatment of venomous snake bites is sometimes difficult for clinicians because sufficient information has not been provided in clinical practice. Here we review the literature to present the proper management of bites by mamushi, habu, and yamakagashi snakes, which widely inhabit Japan and other Asian countries. No definite diagnostic markers or kits are available for clinical practice; therefore, definitive diagnosis of snake-venom poisoning requires positive identification of the snake and observation of the clinical manifestations of envenomation. Mamushi (Gloydius blomhoffii) bites cause swelling and pain that spreads gradually from the bite site. The platelet count gradually decreases due to the platelet aggregation activity of the venom and can decrease to <100,000/mm3. If the venom gets directly injected into the blood vessel, the platelet count rapidly decreases to <10,000/mm3 within 1 h after the bite. Habu (Protobothrops flavoviridis) bites result in swelling within 30 min. Severe cases manifest not only local signs but also general symptoms such as vomiting, cyanosis, loss of consciousness, and hypotension. Yamakagashi (Rhabdophis tigrinus) bites induce life-threatening hemorrhagic symptoms and severe disseminated intravascular coagulation with a fibrinolytic phenotype, resulting in hypofibrinogenemia and increased levels of fibrinogen degradation products. Previously recommended first-aid measures such as tourniquets, incision, and suction are strongly discouraged. Once airway, breathing, and circulation have been established, a rapid, detailed history should be obtained. If a snake bite is suspected, hospital admission should be considered for further follow-up. All venomous snake bites can be effectively treated with antivenom. Side effects of antivenom should be prevented by sufficient preparation. Approved antivenoms for mamushi and habu are available. Yamakagashi antivenom is used as an off-label drug in Japan, requiring clinicians to join a clinical research group for its use in clinical practice.

Impact of neurointensivist-managed intensive care unit implementation on patient outcomes after aneurysmal subarachnoid hemorrhage

PURPOSEnThe purpose of the study is to evaluate the impact of neurointensivist-managed intensive care unit (NIM-ICU) implementation for patients admitted with aneurysmal subarachnoid hemorrhage (SAH).nnnMETHODSnThis study retrospectively evaluated 234 patients (mean age, 61.7 years; male, 67) admitted with SAH between January 1, 2001, and March 31, 2014. Neurologic outcomes between patients admitted from January 2001 to December 2006 (intensivist-managed intensive care unit group) and January 2007 to March 2014 (NIM-ICU group) were compared. The primary outcome was the incidence of a good neurologic outcome at discharge (GO; the modified Ranking Scale score: GO, 0-2; poor neurological outcome, 3-6) at discharge.nnnRESULTSnNeurointensivist-managed intensive care unit was initiated for 151 (64.5%) of 234 patients. Univariate analysis demonstrated significantly better outcomes for NIM-ICU group vs intensivist-managed intensive care unit group (GOs, 58.3% vs 41.0%, respectively, P = .01). Multivariate logistic regression was used to evaluate NIM-ICU efficacy for SAH patients, but NIM-ICU was not significantly associated with GOs (P = .054). Subgroup analysis of patient grading by Hunt and Kosnik grades I to II showed that NIM-ICU implementation was an independent predictor of GOs (odds ratio, 4.54; 95% confidence interval, 1.08-22.17; P = .04).nnnCONCLUSIONnNeurointensivist-managed intensive care unit may improve neurologic outcomes in SAH patients with Hunt and Kosnik grades I to II.

Magnetic resonance imaging and positron emission tomography findings in status epilepticus following severe hypoglycemia

We recently experienced a case with asymmetrical cortical abnormality on MRI with focal status epilepticus following severe hypoglycemia. The cerebral blood flow and metabolisms for oxygen and glucose were determined using positron emission tomography (PET) during focal status epilepticus following severe hypoglycemia and at the follow-up period. Prolonged seizure activity produced profound glucose hypermetabolism and mild hyperemia in the region of the presumed cortical focus of epilepsy and in structures anatomically remote from the focus, corresponding to the areas of abnormal signal intensity on the MRI. The patient remained comatose and exhibited a diffuse hypoperfusion/ hypometabolism and symmetrical brain atrophy on the follow-up PET and MRI, respectively. Cytotoxic brain edema due to profound glucose metabolism without compensatory increase of the blood flow during status epilepticus may account for the brain abnormality observed on the early MRI. Simultaneous examination of the cerebral blood flow and metabolism using PET can provide useful information about the pathology in patients with status epilepticus.

Neurocritical care update

This update comprises six important topics under neurocritical care that require reevaluation. For post-cardiac arrest brain injury, the evaluation of the injury and its corresponding therapy, including temperature modulation, is required. Analgosedation for target temperature management is an essential strategy to prevent shivering and minimizes endogenous stress induced by catecholamine surges. For severe traumatic brain injury, the diverse effects of therapeutic hypothermia depend on the complicated pathophysiology of the condition. Continuous electroencephalogram monitoring is an essential tool for detecting nonconvulsive status epilepticus in the intensive care unit (ICU). Neurocritical care, including advanced hemodynamic monitoring, is a fundamental approach for delayed cerebral ischemia following subarachnoid hemorrhage. We must be mindful of the high percentage of ICU patients who may develop sepsis-associated brain dysfunction.

Effect of admission glasgow coma scale motor score on neurological outcome in out-of-hospital cardiac arrest patients receiving therapeutic hypothermia

BACKGROUNDnBecause the initial (on admission) Glasgow Coma Scale (GCS) examination has not been fully evaluated in comatose survivors of cardiac arrest (CA) who receive therapeutic hypothermia (TH), the aim of the present study was to determine any association between the admission GCS motor score and neurologic outcomes in patients with out-of-hospital CA who receive TH.nnnMETHODSANDRESULTSnIn the J-PULSE-HYPO study registry, patients with bystander-witnessed CA were eligible for inclusion. Patients were divided into 3 groups based on GCS motor score (1, 2-3, and 4-5) to assess various effects on neurologic outcome. Univariate and multivariate analyses were performed to identify independent predictors of good neurologic outcome at 90 days. Of 452 patients, 302 were enrolled. There was a significant difference among the 3 patient groups with regard to neurologic outcome at 90 days in the univariate analysis. Multiple logistic regression analyses showed that the GCS motor score on admission, age >65 years, bystander cardiopulmonary resuscitation, the time from collapse to return of spontaneous circulation, and pupil size <4 mm were independent predictors of a good neurologic outcome at 90 days in cases of CA (GCS motor score, 4-5: odds ratio, 8.18; 95% confidence interval: 1.90-60.28; P<0.01).nnnCONCLUSIONSnGCS motor score is an independent predictor of good neurologic outcome at 90 days in patients sustaining out-of-hospital CA who receive TH.

The impact of age on outcomes of elderly ED patients ventilated due to community acquired pneumonia

OBJECTIVESnThere is no consensus on whether mechanical ventilation should be initiated for advanced age with community-acquired pneumonia (CAP). This study investigated the effects of age on the outcomes of mechanical ventilation in the emergency department (ED) for advanced age with CAP.nnnMETHODSnWe retrospectively investigated the medical records of advanced age (age, ≥65 years) with CAP who required mechanical ventilation in the ED of our hospital between January 2006 and December 2012. The patients were divided into 65 to 74, 75 to 84, and 85 years or older age groups. The following outcomes were measured: number of patients weaned from mechanical ventilation, in-hospital mortality, ventilator-free days, and intensive care unit days. Multiple logistic regression analysis was used to identify risk factors associated with mortality and weaning from mechanical ventilation.nnnRESULTSnSeventy-one patients (mean age, 79.5 years) were included. The overall in-hospital mortality rate was 43.7%. No significant differences were observed among the 3 groups with regard to weaning from mechanical ventilation (P=.59), in-hospital mortality (P=.90), ventilator-free days (P=.83), or intensive care unit days (P=.12). Age was not significantly associated with weaning from mechanical ventilation or in-hospital mortality among advanced age. Diabetes mellitus was an independent factor for weaning from mechanical ventilation (P=.048) and was relatively associated with mortality (P=.051).nnnCONCLUSIONSnAge, in itself, may not be a factor limiting the initiation of mechanical ventilation in the ED in advanced age with CAP. Further studies should determine appropriate indications for mechanical ventilation in the ED for these patients.

Clinical characteristics of yamakagashi (Rhabdophis tigrinus) bites: a national survey in Japan, 2000–2013

BackgroundYamakagashi (Rhabdophis tigrinus) is a species of pit viper present throughout Russia and Eastern Asia. Although R. tigrinus venom is known to induce life-threatening hemorrhagic symptoms, the clinical characteristics and effective treatment of R. tigrinus bites remain unknown. The present study aimed to clarify these issues.MethodsRecords in the Japan Snake Institute between 2000 and 2013 were retrospectively investigated. The following were determined: patient characteristics, coagulation and fibrinolytic system abnormalities, effect of antivenom treatment, and outcomes.ResultsNine patients (all males; median age, 38xa0years) with R. tigrinus bites were identified. On admission, the median levels of fibrinogen and fibrinogen degradation products, and platelet counts were 50xa0mg/dL, 295xa0μg/mL, and 107,000/mm3, respectively. The median (minimum–maximum) disseminated intravascular coagulation (DIC) score defined by the Japanese Association of Acute Medicine was 8 (1–8). Antivenom was administered to seven patients, with a median interval of 35xa0h between bite and antivenom administration. All patients treated with antivenom survived, and the in-hospital mortality rate was 11%.ConclusionsPatients with R. tigrinus bites presented with DIC of a fibrinolytic phenotype, which can result in life-threatening injury unless appropriate antivenom and DIC treatment are provided.