Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients

Alpha2-macroglobulin is a protease inhibitor that enhances procoagulant properties via the neutralization of plasmin, plasminogen activators and metalloproteinases. Additionally, alpha2-macroglobulin is thought to be involved in inflammatory reactions as a carrier protein for interleukin-6 (IL-6). The objective of this study was to evaluate the usefulness of alpha2-macroglobulin as a biomarker for cerebrovascular diseases. Patients with acute ischemic stroke (n = 159; 93 male and 66 female, 71.6 ± 10.3 years) and patients with no previous history of stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. White matter lesions were assessed via the fluid-attenuated inversion recovery image of magnetic resonance images using the Fazekas classification. The serum alpha2-macroglobulin levels were measured by nephelometry. The serum alpha2-macroglobulin levels at admission in patients with acute ischemic stroke were higher than those in the control patients (230.2 ± 73.7 vs. 205.0 ± 55.8 mg/dl, p = 0.009). The serum alpha2-macroglobulin levels were positively correlated with age and the severity of the white matter lesions (R ² = 0.048, p < 0.001 and R ² = 0.058, p < 0.001, respectively), although there was no significant association between serum alpha2-macroglobulin levels and IL-6 levels. In addition, multivariate analysis showed that increased serum alpha2-macroglobulin levels were independently associated with the severity of white matter lesions [standardized partial regression coefficient (β) 0.102, p = 0.026]. Increased serum alpha2-macroglobulin levels might be involved in the pathophysiology of acute ischemic stroke. Furthermore, serum alpha2-macroglobulin levels, which were associated with high-grade white matter lesions, may reflect the chronic pathophysiological condition of cerebral small vessel disease.     

How can epidemiological studies contribute to understanding autism spectrum disorders?

More and more studies on the frequency of autism spectrum disorders (ASD) have been published recently, most of which show the increase in prevalence data. In this review, the author pointed out factors and parameters to be considered in analyzing frequency data, i.e., the enlargement of the concept of autism, prevalence and incidence, accuracy and precision in the initial screening, and the effect of the “vaccine debate”. The proportion of high-functioning ASD has been growing higher and higher due to better recognition in the last few years, and the apparent increase might still be the tip of an iceberg. Future epidemiological studies should include themes on diversity of the longitudinal course and re-conceptualization of ASD by dimensional diagnosis.     

ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)^H46R rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins—inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1^H46R rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1^H46R rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.     

Contrast-enhanced sonography of pancreatic ductal carcinoma using agent detection imaging

Purpose The aim of this study was to evaluate the enhancement behavior of pancreatic ductal carcinoma by contrast-enhanced sonography with agent detection imaging (ADI), and to clarify the origin of microbubble signals by comparisons with histological findings of resected specimens. Methods The subjects were 21 patients with resectable pancreatic carcinoma. The final histological diagnosis was tubular adenocarcinoma in 20 cases, and anaplastic carcinoma in one case. Ultrasound examinations were performed using an Acuson Sequoia 512 series system, and the contrast agent (Levovist) was injected intravenously in doses of 7 ml (300 mg/ml). The ADI signals (in the tumor) were recorded continuously for 30 s after an injection of Levovist (vascular image) and then obtained intermittently (30 s time-intervals) until the signal had diminished in pancreatic tissue (perfusion image). Results Contrast enhancement of the tumor was observed in 71.4% of subjects on the vascular image and 76.3% of subjects on the perfusion image. Enhancement patterns on the vascular image were classified into three types: VI-1 (linear enhancement), VI-2 (spotty enhancement), and VI-3 (no enhancement). VI-1, VI-2, and VI-3 were seen in 9 (42.8%), 6 (28.6%), and 6 (28.6%) of the 21 cases, respectively. Enhancement patterns on the perfusion image were classified into four types: PI-1 (diffuse uneven enhancement), PI-2 (spotty enhancement), PI-3 (peripheral enhancement), and PI-4 (negative enhancement). The incidence of PI-1, PI-2, PI-3, and PI-4 was 4.8%, 42.9%, 28.6%, and 23.8%, respectively. With respect to resectable cases, these enhancement patterns were compared with histological findings, i.e., the distribution of blood vessels in the tumor, remaining pancreatic tissues in the tumor, differentiation of types of adenocarcinoma, volume of stroma, and invasion types of carcinoma. The enhanced patterns consequently corresponded to either the distribution of the blood vessels or the remaining pancreatic tissues in the tumor. Conclusion This study indicated that pancreatic ductal carcinoma is frequently enhanced by microbubbles, and the signals seem to originate from fine blood vessels and the remaining pancreatic tissues in the tumor.     

Attitudes toward the performance of bystander cardiopulmonary resuscitation in Japan

BACKGROUND: Early initiation of bystander cardiopulmonary resuscitation (CPR) improves the chances of successful resuscitation and survival. The importance of bystander CPR is attracting more interest, and there has been an increase in attendance at CPR training courses in Japan. However, there have been few reports regarding Japanese attitudes toward the performance of bystander CPR. The present study was performed to identify current Japanese attitudes toward bystander CPR compared to our previous study performed in 1998. METHODS AND RESULTS: Between February and March 2006, participants were asked about their willingness to perform CPR in five varying scenarios, i.e., performing CPR on a stranger, a trauma patient, a child, an elderly person, and a relative, and CPR techniques consisting of chest compression plus mouth-to-mouth ventilation (CC plus MMV) versus chest compression only (CC only). A total of 4223 individuals (male 50%) completed the questionnaire, including high school students, teachers, emergency medical technicians (EMTs), medical nurses, and medical students. About 70% of the subjects had experienced CPR training more than once. Only 10-30% of high school students, teachers, and health care providers reported willingness to perform CC plus MMV, especially on a stranger or trauma victim. In contrast, 70-100% of these subjects reported willingness to perform CC only, which was the same as in our previous study. The reasons for the unwillingness among laypeople to perform CC plus MMV were inadequate knowledge and/or doubt regarding whether they could perform the techniques effectively, while health care providers reported a fear contracting of a disease. CONCLUSIONS: Most laypeople and health care providers are unlikely to perform CC plus MMV, especially on a stranger or trauma victim, but are more likely to perform CC only, as also found in our previous study in 1998. These findings suggest that MMV training should be de-emphasised and the awareness of CC alone should be emphasised because, for whatever reason, people do not want to perform MMV.     

Length of mechanical restraint following haloperidol injections versus oral atypical antipsychotics for the initial treatment of acute schizophrenia: A propensity-matched analysis from the Japanese diagnosis procedure combination database

Differences in effectiveness between haloperidol injection and oral atypical antipsychotics in the acute-phase treatment of schizophrenia are not well examined. We retrospectively investigated whether these treatment options affected the length of mechanical restraint. We used the Japanese Diagnosis Procedure Combination Database to identify schizophrenia patients who were involuntarily hospitalized and receiving mechanical restraint between July and December, 2006–2009. Data included patient demographics, use of antipsychotics, and number of days on which patients underwent mechanical restraint. Propensity score matching was performed to compare the number of days of mechanical restraint between the haloperidol injection group and the oral atypical antipsychotics group. We used survival analysis to examine whether the initial difference in treatment affected the number of days of mechanical restraint. Cox regression was performed to compare the concurrent effects of various factors. Among 1731 eligible patients, 574 were treated with haloperidol injections and 420 with atypical antipsychotics. Matching produced 274 patients in each group. Cox regression analysis showed that the initial therapeutic agents did not significantly affect the number of days of mechanical restraint. The results indicate that atypical antipsychotics were as effective as haloperidol injections in the acute-phase treatment of schizophrenia.     

Immune-related adverse events and prognosis in patients with upper gastrointestinal cancer treated with nivolumab

BackgroundImmune checkpoint inhibitors (ICIs) are increasingly being used for the treatment of upper gastrointestinal cancers [esophageal cancer and gastric cancer (GC)]. They cause imbalances in immunological tolerance, resulting in immune-related adverse events (irAEs). Although irAEs have been reported to be associated with the efficacy of ICIs in some cancers, the relationship between irAEs and prognosis of upper gastrointestinal cancers remains unknown. This study aimed to investigate the prognostic impact of irAEs in patients with advanced or recurrent upper gastrointestinal cancer treated with nivolumab.MethodsWe retrospectively divided the patients (n=96) who received nivolumab into two groups: the irAEs group (n=41) and non-irAEs group (n=55), according to the Common Terminology Criteria for Adverse Events ver. 5.0.ResultsirAEs were significantly associated with good performance status and high serum albumin levels (all P<0.05). The irAEs group had a significantly longer overall survival (OS) than the non-irAEs group [log-rank P=0.003; univariate hazard ratio (HR) =0.36, 95% confidence interval (CI) =0.21–0.65, P<0.01; multivariate HR =0.47, 95% CI =0.26–0.88, P=0.018]. Importantly, in both esophageal cancer and GC, the irAEs group experienced favorable clinical outcomes compared with the non-irAEs group. In the multivariate analysis, male sex (P<0.01), presence of irAEs (P=0.018), and good pretreatment performance status (P<0.01) were independent prognostic factors.ConclusionsAmong patients with upper gastrointestinal cancer treated with nivolumab, the prognosis of patients who developed irAEs was better than that of patients who did not develop irAEs. Long-term continuation of nivolumab by early detection of irAEs and an appropriate response to irAEs are important.