Access to mechanical thrombectomy and ischemic stroke mortality in Japan: a spatial ecological study

BackgroundAdvances in stroke treatment have greatly improved outcomes; however, disparities in access to treatment might increase. Achieving equitable access to stroke treatment is a health policy challenge, as rapid treatment is essential for positive outcomes. This ecological cross-sectional study aimed to determine the relationship between the disparities in spatial accessibility to mechanical thrombectomy (SAMT) and stroke mortality rates in Japan, hypothesizing that disparities in SAMT may increase the differences in stroke mortality between regions.MethodsWe used the average number of ischemic stroke (IS) deaths between 2020 and 2021 as the response variable; and SAMT, medical resources, and socioeconomic characteristics of each municipality as explanatory variables. A conditional autoregressive model was used to examine the association between the risk of stroke mortality and SAMT. The standardized mortality ratio (SMR) was mapped to understand the nationwide disparities in stroke mortality risk.ResultsThe median number of IS deaths was 17.5 persons per year in the municipalities (2020 to 2021). The study also found that municipalities with low SAMT were located in the northern part of Japan. The non-spatial regression model results indicated that poor accessibility, a small proportion of bachelor’s degrees or higher, and a high proportion of workers in secondary industries were related to high IS mortality. Three models were evaluated using spatial analysis; Model 1 with accessibility indicators alone, Model 2 with medical resources added to Model 1, and Model 3 with socioeconomic characteristics added to Model 2. In Models 1 and 2, the population-weighted spatial accessibility index (PWSAI) showed a significant negative relationship with stroke mortality. However, this was not evident in Model 3. Mapping using Model 3 showed that the high-risk areas were predominantly located in northern Japan, excluding Hokkaido.ConclusionAccess to mechanical thrombectomy was estimated, and regional differences were observed. The relationship between accessibility and IS mortality is unknown; however, regardless of accessibility, municipalities with a high proportion of workers in secondary industries and a small proportion with bachelor’s degrees or above are at risk of death from stroke

Three-Dimensional Quantitative Assessment of Ablation Margins Based on Registration of Pre- and Post-Procedural MRI and Distance Map

Purpose: Contrast-enhanced MR images are widely used to confirm the adequacy of ablation margin after liver ablation for early prediction of local recurrence. However, quantitative assessment of the ablation margin by comparing pre- and post-procedural images remains challenging. We developed and tested a novel method for three-dimensional quantitative assessment of ablation margin based on non-rigid image registration and 3D distance map. Methods: Our method was tested with pre- and post-procedural MR images acquired in 21 patients who underwent image-guided percutaneous liver ablation. The two images were co-registered using non-rigid intensity-based registration. After the tumor and ablation volumes were segmented, target volume coverage, percent of tumor coverage, and Dice Similarity Coefficient were calculated as metrics representing overall adequacy of ablation. In addition, 3D distance map around the tumor was computed and superimposed on the ablation volume to identify the area with insufficient margins. For patients with local recurrences, the follow-up images were registered to the post-procedural image. Three-D minimum distance between the recurrence and the areas with insufficient margins were quantified. Results: The percent tumor coverage for all non-recurrent cases was 100%. Five cases had tumor recurrences, and the 3D distance map revealed insufficient tumor coverage or a 0-millimeter margin. It also showed that two recurrences were remote to the insufficient margin. Conclusions: Non-rigid registration and 3D distance map allows us to quantitatively evaluate the adequacy of the ablation margin after percutaneous liver ablation. The method may be useful to predict local recurrences immediately following ablation procedure

ショクドウ ソウカン ニヨル フンゴウブ カンゼン リカイ オ カイケッチョウ サイケン デ シュウフクシタ ショクドウ セツジョ ノ 1レイ

症例は60 歳代, 男性. 身長162.6 cm, 体重40.0 kg, Body Mass Index（BMI）15.1 kg / m2であり, 既往歴に慢性閉塞性肺疾患（COPD）を認めた. 胸部上部食道癌 T1b N0 M0 Stage Iに対して食道亜全摘, 3領域リンパ節郭清, 胸骨後胃管再建を施行した.術当日に抜管したが, 術後肺炎に伴う呼吸不全のため, 術後6日目に気管内挿管を試みたが、食道挿管となった．再挿管, 人工呼吸管理の後に軽快し術後13日目に抜管となったが, 術後透視で吻合部周囲に造影剤漏出を認めた. 2ヶ月間の保存的加療で造影剤漏出は消失したが吻合部に長径4 cmの高度狭窄を認めた．内視鏡的拡張術での改善は困難であり, 術後243日目に消化管再建術を施行した. 手術所見として, 第2肋間より頭側の胸骨を切除したところ, 胃管の口側断端は第2肋間の高さの胸骨後面に位置していた.食道断端までは肉芽で置換されていた.胸骨前経路回結腸再建を施行し, 再建術後 8日目に食事を開始し, 合併症なく再建術後30日目に退院となった. 回結腸再建後2年経過後も食道癌の再発は認めず, 通過障害なく経口摂取のみでの生活が可能となっている．A 60s-year-old man underwent endoscopic screening during which a tumor was detected in the upper thoracic esophagus, which was diagnosed as T1bN0M0 Stage I esophageal squamous cell carcinoma. He had a history of chronic obstructive pulmonary disease. He underwent subtotal esophagectomy with 3 field lymph node dissection. Reconstruction was performed by gastric tube through the posterior sternal route. Extubation was performed on the day of surgery. Respiratory failure by postoperative pneumonia occurred, and ventilatory management was performed on the sixth postoperative day. However, the intubation was put into the esophagus. He became well and extubation was performed on the 13th postoperative day. Postoperative fluoroscopy showed contrast leakage around the anastomotic site. After 2 months of conservative treatment, the contrast leak disappeared, but there was a severe stenosis of 4 cm in length at the anastomosis. Endoscopic dilatation was not sufficient to improve the stenosis. Gastrointestinal reconstruction was performed on the 243rd postoperative day. The cephalic sternum was resected, and the gastrointestinal canal opening margin was located on the posterior surface of the sternum, at the level of the second intercostal space. The segment was replaced by a granulation. The patient underwent anterior sternal ileocolic reconstruction. Oral intake started on the 8th day after the reconstruction, and hospital discharge was on the 30 th day after the reconstruction without any complications. Two years after ileocolic reconstruction, there has been no cancer recurrence, and he lives well on oral intake only

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Simple Breeding Method and Basic Biology of Campsomeris annulata（ Hymenoptera: Scoliidae）

緒言 材料と方法 結果 考察 要約本研究ではコガネムシ類の幼虫に対する天敵であるヒメハラナガツチバチの簡易飼育法及び基礎生態について調べた．ヒメハラナガツチバチの成虫は，25%のハチミツを与える事で飼育する事ができ，採卵については，直径12cmほどのカップに，煮沸消毒したのち冷まして水をよく絞った水苔を薄く詰め，そこに雌とドウガネブイブイの3 齢幼虫を1 匹ずつ入れて暗所に１日置く事で卵を得る事が出来た．越冬明けの雌の平均産卵数は23.63 ± 10.77 個で，平均寿命は37.00 ±15.96 日であった．また，卵を20℃，25℃，30℃で飼育し，有効積算温量と発育零点を算出したところ，それぞれ433.5 日度， 15.08℃であった．成虫までの死亡率は，20℃で72.3%，25℃で49.3%，30℃では57.1%であり，20℃で有意に高い傾向が見られた．また，25℃と30℃では，産卵日時の遅い個体ほど，死亡率が高くなる傾向が見られた．成虫の寿命は，雄が平均72.18 ± 42.14 日，雌が平均95.30 ± 55.20 日で，雌が有意に長かった．また幼虫期に20℃で飼育した個体では，25℃，30℃で飼育した個体に比べて有意に寿命が短い傾向が見られた.Campsomeris annulata （Hymenoptera: Scoliidae） is an important natural enemy of scarabaeid beetle grubs. However, few studies have addressed their effective rearing procedure and basic biology, so far. We developed the simple breeding method and investigated the basic biology of C. annulata. The last instar grubs of Anomala cuprea were used as a suitable host of C. annulata. An oviposition by female C. annulata was induced with a host grub and the sphagnum moss in a plastic cup, which was kept under a constant dark environment for one night. Overwintered females collected from the field oviposited an average of 23.63±10.77（ SD） eggs during their lifetime when kept at 25℃ . Their average longevity was 37.00 ± 15.96 days. Developmental threshold temperature and thermal constant of C. annulata were 15.08 ℃ and 433.5 degree day, respectively. The mortalities during the immature development were 72% , 49% and 57.1% at 20℃ , 25℃ and 30℃ , respectively. The mortality was significantly high at 20℃ . Curiously, under 25℃ and 30℃ conditions, the offspring mortality was significantly higher when they were laid later in the mothers’ life. The longevities of adult wasps in the 25℃ 16L8D condition were an average of 72.18 ± 42.14 days in males and 95.30 ± 55.20 days in females; females lived significantly longer than males. The longevity of the wasps that had bred at 20℃ during the immature development was shorter than those at 25℃ and 30℃ . The current results complement the previous fragmentary field observations of C. annulata and help the understanding of its general biology

Three-dimensional quantitative assessment of ablation margins based on registration of pre- and post-procedural MRI and distance map.

PURPOSE: Contrast-enhanced MR images are widely used to confirm the adequacy of ablation margin after liver ablation for early prediction of local recurrence. However, quantitative assessment of the ablation margin by comparing pre- and post-procedural images remains challenging. We developed and tested a novel method for three-dimensional quantitative assessment of ablation margin based on non-rigid image registration and 3D distance map. METHODS: Our method was tested with pre- and post-procedural MR images acquired in 21 patients who underwent image-guided percutaneous liver ablation. The two images were co-registered using non-rigid intensity-based registration. After the tumor and ablation volumes were segmented, target volume coverage, percent of tumor coverage, and Dice similarity coefficient were calculated as metrics representing overall adequacy of ablation. In addition, 3D distance map around the tumor was computed and superimposed on the ablation volume to identify the area with insufficient margins. For patients with local recurrences, the follow-up images were registered to the post-procedural image. Three-dimensional minimum distance between the recurrence and the areas with insufficient margins was quantified. RESULTS: The percent tumor coverage for all nonrecurrent cases was 100 %. Five cases had tumor recurrences, and the 3D distance map revealed insufficient tumor coverage or a 0-mm margin. It also showed that two recurrences were remote to the insufficient margin. CONCLUSIONS: Non-rigid registration and 3D distance map allow us to quantitatively evaluate the adequacy of the ablation margin after percutaneous liver ablation. The method may be useful to predict local recurrences immediately following ablation procedure

ヒメハラナガツチバチ Campsomeris annulata の簡易飼育法と基礎生態

本研究ではコガネムシ類の幼虫に対する天敵であるヒメハラナガツチバチの簡易飼育法及び基礎生態について調べた．ヒメハラナガツチバチの成虫は，25%のハチミツを与える事で飼育する事ができ，採卵については，直径12cmほどのカップに，煮沸消毒したのち冷まして水をよく絞った水苔を薄く詰め，そこに雌とドウガネブイブイの3 齢幼虫を1 匹ずつ入れて暗所に１日置く事で卵を得る事が出来た．越冬明けの雌の平均産卵数は23.63 ± 10.77 個で，平均寿命は37.00 ±15.96 日であった．また，卵を20℃，25℃，30℃で飼育し，有効積算温量と発育零点を算出したところ，それぞれ433.5 日度， 15.08℃であった．成虫までの死亡率は，20℃で72.3%，25℃で49.3%，30℃では57.1%であり，20℃で有意に高い傾向が見られた．また，25℃と30℃では，産卵日時の遅い個体ほど，死亡率が高くなる傾向が見られた．成虫の寿命は，雄が平均72.18 ± 42.14 日，雌が平均95.30 ± 55.20 日で，雌が有意に長かった．また幼虫期に20℃で飼育した個体では，25℃，30℃で飼育した個体に比べて有意に寿命が短い傾向が見られた.Campsomeris annulata （Hymenoptera: Scoliidae） is an important natural enemy of scarabaeid beetle grubs. However, few studies have addressed their effective rearing procedure and basic biology, so far. We developed the simple breeding method and investigated the basic biology of C. annulata. The last instar grubs of Anomala cuprea were used as a suitable host of C. annulata. An oviposition by female C. annulata was induced with a host grub and the sphagnum moss in a plastic cup, which was kept under a constant dark environment for one night. Overwintered females collected from the field oviposited an average of 23.63±10.77（ SD） eggs during their lifetime when kept at 25℃ . Their average longevity was 37.00 ± 15.96 days. Developmental threshold temperature and thermal constant of C. annulata were 15.08 ℃ and 433.5 degree day, respectively. The mortalities during the immature development were 72% , 49% and 57.1% at 20℃ , 25℃ and 30℃ , respectively. The mortality was significantly high at 20℃ . Curiously, under 25℃ and 30℃ conditions, the offspring mortality was significantly higher when they were laid later in the mothers’ life. The longevities of adult wasps in the 25℃ 16L8D condition were an average of 72.18 ± 42.14 days in males and 95.30 ± 55.20 days in females; females lived significantly longer than males. The longevity of the wasps that had bred at 20℃ during the immature development was shorter than those at 25℃ and 30℃ . The current results complement the previous fragmentary field observations of C. annulata and help the understanding of its general biology.緒言 材料と方法 結果 考察 要