Yoshitaka Nishikawa

Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance

Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110γ (Pik3cg−/−), the catalytic subunit of PI3Kγ, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg−/− mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kγ can be a therapeutic target for type 2 diabetes.

Physical performance deterioration of temporary housing residents after the Great East Japan Earthquake

Disaster has a negative impact on health conditions, especially on those of temporary housing residents. Health status has a close relationship with physical activity and performance. However, few reports have assessed physical performance among residents living in temporary housing. In this study, we compared physical capabilities between the elderly who evacuated to temporary housing and those who stayed in their own homes after the Great East Japan Earthquake. Subjects were recruited from those over 65 years of age who participated in the medical check-ups for temporary housing residents (TH group) or check-ups for residents of downtown areas (control group) in Soma City, Fukushima, in 2012. The subjects underwent grip strength, one-leg standing (OLS), and timed up and go tests (TUG). In total, 1890 participants were recruited. The TH group showed significantly stronger grip strength than that of the control group. On the other hand, the TH group showed weaker standing stability, according to decreased OLS and increased TUG scores. We revealed that standing stability was impaired among elderly temporary housing residents 1.5 years after the disaster. Disaster responders should take into account the health risks associated with living in temporary housing.

Post-nuclear disaster evacuation and survival amongst elderly people in Fukushima: A comparative analysis between evacuees and non-evacuees

BACKGROUND Considering the health impacts of evacuation is fundamental to disaster planning especially for vulnerable elderly populations; however, evacuation-related mortality risks have not been well-investigated. We conducted an analysis to compare survival of evacuated and non-evacuated residents of elderly care facilities, following the Great East Japan Earthquake and subsequent Fukushima Dai-ichi nuclear power plant incident on 11th March 2011. OBJECTIVE To assess associations between evacuation and mortality after the Fukushima nuclear incident; and to present discussion points on disaster planning, with reference to vulnerable elderly populations. METHODS The study population comprised 1,215 residents admitted to seven elderly care facilities located 20-40km from the nuclear plant in the five years before the incident. Demographic and clinical characteristics were obtained from medical records. Evacuation histories were tracked until mid 2013. Main outcome measures are hazard ratios in evacuees versus non-evacuees using random-effects Cox proportional hazards models, and pre- and post-disaster survival probabilities and relative mortality incidence. RESULTS Experiencing the disasters did not have a significant influence on mortality (hazard ratio 1.10, 95% confidence interval: 0.84-1.43). Evacuation was associated with 1.82 times higher mortality (95% confidence interval: 1.22-2.70) after adjusting for confounders, with the initial evacuation from the original facility associated with 3.37 times higher mortality risk (95% confidence interval: 1.66-6.81) than non evacuation. CONCLUSIONS The government should consider updating its requirements for emergency planning for elderly facilities and ensure that, in a disaster setting, these facilities have the capacity and support to shelter in place for at least sufficient time to adequately prepare initial evacuation.

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)–4.29 mSv), 0.37 mSv (range: ND–3.61 mSv), 0.22 mSv (range: ND–1.44 mSv), 0.20 mSv (range: ND–1.87 mSv), and 0.17 mSv (range: ND–0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04–0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses.

Managing Type 2 Diabetes Mellitus through Periodical Hospital Visits in the Aftermath of the Great East Japan Earthquake Disaster: A Retrospective Case Series

Aims To assess the impact of the Great East Japan Earthquake Disaster on daily diabetes practice and to determine the feasibility of controlling type 2 diabetes mellitus in an outpatient department. Methods We retrospectively reviewed the data on disaster-affected patients with type 2 diabetes who periodically attended outpatient department of Soma Central Hospital. There were 767 patients with type 2 diabetes mellitus in total. The primary outcome measure was the change in HbA1c. Results HbA1c levels of 58 patients with periodical hospital visits did not deteriorate after the disasters. Moreover, there observed no significant difference in the mean of HbA1c levels among all age and sex throughout the year. While several changes in diabetes medication usage occurred, DPP4-inhibitor was the only oral diabetic agent that increased in frequency (+60%). Conclusions Patients with type 2 diabetes who were managed with periodical hospital visits did not show significant deterioration in HbA1c levels.

Towards a Long-Term Strategy for Voluntary-Based Internal Radiation Contamination Monitoring: A Population-Level Analysis of Monitoring Prevalence and Factors Associated with Monitoring Participation Behavior in Fukushima, Japan

Following Japan’s 2011 Fukushima nuclear incident, we assessed voluntary-based monitoring behavior in Minamisoma City—located 10–40 km from the Fukushima nuclear plant—to inform future monitoring strategies. The monitoring in Minamisoma included occasional free of charge internal-radiation-exposure measurements. Out of around 70,000 individuals residing in the city before the incident, a total of 45,788 residents (female: 52.1%) aged ≥21 were evaluated. The monitoring prevalence in 2011–2012 was only 30.2%, and this decreased to 17.9% in 2013–2014. Regression analyses were performed to estimate factors associated with the monitoring prevalence and participation behavior. The results show that, in comparison with the age cohort of 21–30 years, the cohort of 71–80 and ≥81 years demonstrated significantly lower monitoring prevalence; female residents had higher monitoring prevalence than male residents; those who were living in evacuation zones at the time of the incident had higher monitoring prevalence than those who lived outside any of the evacuation zones; for those living outside Fukushima and neighboring Prefectures post-incident monitoring prevalence decreased significantly in 2013–2014. Our findings inform the discussion on the concepts of radiation risk perception and accessibility to monitoring and societal decision-making regarding the maintenance of the monitoring program with low monitoring prevalence. We also stress the possibility that the monitoring can work both to check that internal contamination levels are within acceptable limits, and as a risk communication tool, alleviating individuals’ concern and anxiety over radiation contamination.

Rituximab-including combined modality treatment for primary thyroid lymphoma: an effective regimen for elderly patients.

BACKGROUND Primary thyroid lymphoma (PTL) develops mostly in middle-aged and older females. However, the optimal treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL), which accounts for most PTL cases, is unclear. Rituximab is a promising drug that, in combination with traditional combination therapy, has demonstrated an increased antitumor effect without a substantial increase in toxicity. In this study, treatment outcomes of elderly patients with thyroid DLBCL who underwent rituximab-including combination therapy were analyzed. METHOD Between January 2005 and December 2011, 43 patients 60 years of age or older (median 71 years, range 60-80 years) were diagnosed as having stage IE (n=12) or stage IIE (n=31) DLBCL, and three courses of R-CHOP therapy (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, adriamycin 40 mg/m2, vincristine 1.4 mg/m2, and prednisolone 100 mg/body) and involved field irradiation were planned. Treatment outcomes of these patients were retrospectively reviewed. RESULTS Two patients terminated the treatment because of interstitial pneumonia during R-CHOP therapy. Only one patient showed treatment resistance and the regimen was changed; 42 patients (98%) responded to the treatment. Five-year overall survival and event-free survival were 87% (95% confidence interval [95% CI], 64-96%) and 74% (95% CI, 50-89%), respectively. CONCLUSION The results of the present study indicate that rituximab-including combination therapy was effective for elderly patients with thyroid DLBCL. A multicenter, long-term observational study is needed to confirm this, and additional refinement of the treatment protocol is required to optimize the antitumor effect.

Acute Remodeling of an Adjoining Aneurysm after Endovascular Treatment of a Ruptured Splanchnic Arterial Aneurysm: A Case of Clinically Diagnosed Segmental Arterial Mediolysis

A 61-year-old woman with multiple splanchnic arterial aneurysms (SAAs) was transferred to our hospital in a state of shock. She underwent coil embolization under the diagnosis of ruptured pancreaticoduodenal artery aneurysm. Follow-up computed tomography performed 2 weeks later showed rapid enlargement of a gastric artery aneurysm, and she underwent an additional embolization. Atherosclerotic, inflammatory or hereditary causes were excluded, and the patient was clinically diagnosed with segmental arterial mediolysis accompanied by multiple SAAs, one of which showed acute remodeling after endovascular treatment.

Application of Convolutional Neural Networks in the Diagnosis of Helicobacter pylori Infection Based on Endoscopic Images

Background and aims The role of artificial intelligence in the diagnosis of Helicobacter pylori gastritis based on endoscopic images has not been evaluated. We constructed a convolutional neural network (CNN), and evaluated its ability to diagnose H. pylori infection. Methods A 22-layer, deep CNN was pre-trained and fine-tuned on a dataset of 32,208 images either positive or negative for H. pylori (first CNN). Another CNN was trained using images classified according to 8 anatomical locations (secondary CNN). A separate test data set (11,481 images from 397 patients) was evaluated by the CNN, and 23 endoscopists, independently. Results The sensitivity, specificity, accuracy, and diagnostic time were 81.9%, 83.4%, 83.1%, and 198 s, respectively, for the first CNN, and 88.9%, 87.4%, 87.7%, and 194 s, respectively, for the secondary CNN. These values for the 23 endoscopists were 79.0%, 83.2%, 82.4%, and 230 ± 65 min (85.2%, 89.3%, 88.6%, and 253 ± 92 min by 6 board-certified endoscopists), respectively. The secondary CNN had a significantly higher accuracy than endoscopists (by 5.3%; 95% CI, 0.3–10.2). Conclusion H. pylori gastritis could be diagnosed based on endoscopic images using CNN with higher accuracy and in a considerably shorter time compared to manual diagnosis by endoscopists.

Towards a Long-Term Strategy for Voluntary-Based Internal Radiation Contamination Monitoring: Representativeness of the Monitoring Results in Fukushima, Japan

Following Japan’s 2011 Fukushima nuclear incident, voluntary participation, rather than mandatory, was adopted as the default scenario for individual radiation monitoring. We evaluated the representativeness of the internal monitoring results from voluntary participants in Minamisoma City, which is located 10–40 km from the Fukushima nuclear plant. Of approximately 70,000 individuals who were residing in Minamisoma City before the incident, a total of 19,263 residents (aged ≥21 years) participated in the monitoring from 1 October 2011 to 31 March 2015. Based on regression projection techniques with the available data obtained from the voluntary participants, the modeled probabilities of radiocesium (Cs) detection in October 2011 for Cs-137 and Cs-134 were 66.9% and 52.9%, respectively, which declined dramatically within a year following the incident. The rate of decline had stagnated since mid-2012, and the probability was close to zero after mid-2014. Sufficient agreement between the modeled probabilities of Cs detection (for the whole population) versus the measured Cs levels (for voluntary participants) was observed, except for Cs-134 in October 2011, indicating that the voluntary monitoring participant group was a good representative sample. Our findings affirmed the clinical importance of voluntary-based monitoring as a screening and dose-assessment tool in a post-nuclear incident. Our study informs societal decision-making regarding the long-term maintenance of the monitoring program under the current low exposure levels.