裂孔原性網膜剥離における強膜バックリング手術後の脈絡膜厚の変化に関する研究

金沢大学附属病院裂孔原性網膜剥離における強膜バックリング手術による眼血流、特に脈絡膜血流への影響が多数報告されている。術後早期から脈絡膜血流が徐々に低下し、術前のレベルまで復帰しないとする報告や、術後3ヶ月までに術前と同レベルへ復帰するとする報告など様々である。これまで脈絡膜の形態的変化を捉えることは困難であったが、近年光干渉断層計(Optical Coherence Tomography, OCT)を用いることにより種々の脈絡膜疾患における脈絡膜の形態的変化を捉えることが可能となった。そこで我々は、裂孔原性網膜剥離における強膜バックリング手術前後の中心脈絡膜厚変化を調べ、術前値に対する術後脈絡膜厚比を調べた。そして術前脈絡膜厚と比較して、術後1週では有意に増加し術後1ヶ月、3ヶ月では術前と同等であることを第65回日本臨床眼科学会、American Journal of Ophthalmologyで報告した。また、我々のこれまでの研究では全例で強膜バックリングおよび冷凍凝固を行っている。裂孔原性網膜剥離における強膜バックリング手術で、凝固手段として術中の冷凍凝固施行群と術後1ヶ月での光凝固施行群での無作為試験の報告では、網膜復位率は同等でありながら冷凍凝固群で有意に術後炎症の増加を認めている。そこで中心脈絡膜厚増加に対する冷凍凝固の影響を排除するために、術中に冷凍凝固を施行せず術前後に同様の検査を行うことにより、バックリング手術自体の脈絡膜循環への影響を検討した。凝固手段としては術後光凝固を施行した。術中に冷凍凝固を施行しなかった場合でも、術前脈絡膜厚と比較して、術後1週では有意に増加し術後1ヶ月、3ヶ月では術前と同等であることを第36回日本眼科手術学会総会で報告した。研究課題/領域番号:24931045, 研究期間(年度):201

Amplification of mutant KRASG12D in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy : a case report

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancer types. Activating oncogenic KRAS mutations are commonly observed in PDAC; however, oncogenic KRAS amplification is rarely observed, and its significance in prognosis and resistance to therapy remains poorly characterized. The present report describes the case of a 52‑year‑old male patient diagnosed with advanced PDAC with liver metastasis. The patient received modified FOLFIRINOX (mFFX) therapy to which the patient became intolerant with a strong inflammatory response. Subsequent treatment with gemcitabine plus nab‑paclitaxel failed to control the disease. Targeted genetic analysis revealed KRASG12D and TP53R248Q mutations in the primary tumor and liver metastases. Analysis of circulating tumor DNA (ctDNA) before the first line of treat‑ ment confirmed these genetic findings and revealed a >4‑fold amplification of the mutant KRASG12D not detected in the primary tumor. Additionally, subsequent analysis confirmed a 5‑fold amplification of the KRASG12D allele in liver metastasis. Consecutive monitoring of ctDNA revealed an initial decrease in the tumor burden 2 weeks after the first cycle of mFFX. However, coinciding with treatment intolerance, a sharp increase in tumor mutational levels and KRASG12D amplifica‑ tion was observed 1 month later. The patient died 70 days after treatment initiation. Overall, amplification of oncogenic KRASG12D was not only associated with an aggressive pheno‑ type, but also supported cancer resistance to chemotherapy. Importantly, this case suggests that plasma detection of KRASG12D amplification is feasible in the clinical routine and constitutes a powerful tool for assessing tumor aggressiveness

Voxel-based correlation of 18F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults

BackgroundsAlthough neurofibrillary tangles (NFTs) mainly accumulate in the medial temporal lobe with human aging, only a few imaging studies have investigated correlations between NFT accumulation and gray matter (GM) volume in cognitively normal older adults. Here, we investigated the correlations between 18F-THK5351 accumulation and GM volume at the voxel level.Material and methodsWe recruited 47 amyloid-negative, cognitively normal, older adults (65.0 ± 7.9 years, 26 women), who underwent structural magnetic resonance imaging, 11C-Pittsburgh compound-B and 18F-THK5351 PET scans, and neuropsychological assessment. The magnetic resonance and 18F-THK5351 PET images were spatially normalized using Statistical Parametric Mapping 12. Voxel-wise correlations between 18F-THK5351 accumulation and GM volume were evaluated using the Biological Parametric Mapping toolbox.ResultsA significant negative correlation (p < 0.001) between 18F-THK5351 accumulation and GM volume was detected in the bilateral medial temporal lobes.ConclusionsVoxel-wise correlation analysis revealed a significant negative correlation between 18F-THK5351 accumulation and GM volume in the medial temporal lobe in individuals without amyloid-β deposits. These results may contribute to a better understanding of the pathophysiology of primary age-related tauopathy in human aging

Changes in serum antibody titers after vaccination for COVID-19 and evaluation of post-vaccination health conditions

　Introduction: The coronavirus disease 2019 (COVID-19) vaccine has preventive effects and high immunogenicity, but the outcomes of vaccination have not been widely reported. The goal of this study was to examine serum antibody titers before and after vaccination and to evaluate post-vaccination health conditions.　Methods: The subjects were 2,304 medical workers (mean age 41 years) at Kawasaki Gakuen who agreed to participate in the study and underwent COVID-19 vaccination, beginning in March 2021. Serum IgG antibody titers for SARS-CoV-2 spike protein were measured before the first vaccination and 4 weeks after the second vaccination. Health conditions were observed for 4 weeks after the second vaccination.　Results: The rates of seroconversion, seroprotection, and change in geometric mean antibody titer at 4 weeks after the second vaccination were 99.9%, 99.9%, and 2,685.5 (95% CI 587.8-5,319.2), respectively, suggesting high immunogenicity. After the first vaccination, pain, enlargement, and reddening occurred at the local injection site, and systemic side effects included fatigue, headache, physical pain, chill, nausea, and fever. After the second vaccination, the incidence of pain decreased, but those of other events increased. There were no serious side effects requiring hospitalization. In logistic regression analysis, sex, age, fever,chill, and lymph node enlargement after the second vaccination were associated with a change in antibody titer.　Conclusions: Serum antibody titers suggested high immunogenicity of the COVID-19 vaccine and a health condition survey confirmed the safety of the vaccine. Systemic side effects may serve as an index of immunization (acquisition of antibody) by the vaccine

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A simple lens-sparing technique to treat hypotonic maculopathy secondary to large cyclodialysis

Purpose: Hypotonic maculopathy secondary to cyclodialysis often persists and causes irreversible visual loss despite a variety of treatments proposed. The purpose of this study is to report two cases with persistent hypotonic maculopathy due to a large cyclodialysis cleft treated with a simple, lens-sparing technique of external drainage, diathermy, and suturing under the placement of an infusion cannula. Observations: Both patients had sustained blunt trauma to one eye, causing persisting hypotonic maculopathy. One eye was phakic. The ciliary body was totally detached with a large cyclodialysis cleft. After half-thickness scleral flaps were made and a 25-gauge infusion cannula was placed at the pars plana, external drainage was performed. Transscleral diathermy and interrupted suturing also were done. Results: In both cases, the ciliary detachment promptly improved and the intraocular pressure normalized after transient elevation for a few days. No adverse events were observed. Conclusions and importance: We successfully treated two cases with hypotonic maculopathy by a simple technique with an infusion cannula. This procedure is simple, immediately effective, less invasive, and applicable to all cases including phakic eyes. Keywords: Blunt trauma, Ciliary body detachment, Cyclodialysis, External drainage, Hypotonic maculopathy, Infusion cannul

The impact of the Tokyo Metropolitan Emissions Trading Scheme on reducing greenhouse gas emissions: findings from a facility-based study

<p>This paper provides a detailed analysis of the Tokyo Metropolitan Emissions Trading Scheme (Tokyo ETS), Japan’s first emissions trading scheme with mandatory cap initiated by the government of Tokyo. Unlike trading schemes in other countries, the Tokyo ETS covers indirect emissions from the commercial sector. It is well known that a variety of market barriers impede full realization of energy efficiency opportunities, especially in the commercial sector. Experiences with the Tokyo ETS should therefore provide important lessons for the design of climate change mitigation policies, especially when targeting the commercial sector. The emissions from covered entities have been drastically reduced from those at the scheme’s outset, with an average 14% reduction as of the end of the first commitment period of five years (2010–2014) compared with 2009 levels. This paper shows that the Tokyo ETS alone did not cause these reductions; there were other drivers. Among them, the energy savings triggered by the Great East Japan Earthquake in 2011 were crucial. The contribution of credit trading, in contrast, was limited since most of the covered entities reduced emissions by themselves. Through an investigation of official reports, an assessment of the emissions data from the covered entities compared to those of uncovered entities and in-depth interviews with firms covered by the scheme, this paper confirms that the main drivers of emissions reductions by covered entities were separate from the ETS. In fact, the advisory aspect of the scheme seems to be much more important in encouraging energy-saving actions.</p> <p><b>Key policy insights</b></p><p>Most of the observed emission reductions were not caused by the Tokyo ETS alone.</p><p>An advisory instrument was crucial to the effectiveness of the Tokyo ETS.</p><p>The experience of the Tokyo ETS suggests that making full use of the advantages of emissions trading is difficult in the case of the commercial sector.</p><p>Price signals have not provided a stimulus to climate change mitigation actions, which implies that establishing a cap to yield effective carbon prices poses a challenge.</p><p></p> <p>Most of the observed emission reductions were not caused by the Tokyo ETS alone.</p> <p>An advisory instrument was crucial to the effectiveness of the Tokyo ETS.</p> <p>The experience of the Tokyo ETS suggests that making full use of the advantages of emissions trading is difficult in the case of the commercial sector.</p> <p>Price signals have not provided a stimulus to climate change mitigation actions, which implies that establishing a cap to yield effective carbon prices poses a challenge.</p