Publications by authors named "Atsushi Hirano"

165 Publications

Protein's Protein Corona: Nanoscale Size Evolution of Human Immunoglobulin G Aggregates Induced by Serum Albumin.

ACS Appl Mater Interfaces 2022 Jul 13. Epub 2022 Jul 13.

Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan.

Nanoparticles are readily coated by proteins in biological systems. The protein layers on the nanoparticles, which are called the protein corona, influence the biological impacts of the nanoparticles, including internalization into cells and cytotoxicity. This study expands the scope of the nanoparticle's protein corona for exogenous artificial nanoparticles to that for exogenous proteinaceous nanoparticles. Specifically, this study addresses the formation of protein coronas on nanoscale human antibody aggregates with a radius of approximately 20-40 nm, where the antibody aggregates were induced by a pH shift from low to neutral pH. The size of the human immunoglobulin G (hIgG) aggregates grew to approximately 25 times the original size in the presence of human serum albumin (HSA). This size evolution was ascribed to the association of the hIgG aggregates, which was triggered by the formation of the hIgG aggregate's protein corona, , protein's protein corona, consisting of the adsorbed HSA molecules. Because hIgG aggregate association was significantly reduced by the addition of 30-150 mM NaCl, it was attributed to electrostatic attraction, which was supported by molecular dynamics (MD) simulations. Currently, the use of antibodies as biopharmaceuticals is concerning because of undesired immune responses caused by antibody aggregates that are typically generated by a pH shift during the antibody purification process. The present findings suggest that nanoscale antibody aggregates form protein coronas induced by HSA and the resulting nanoscale antibody-HSA complexes are stable in blood containing approximately 150 mM salt ions, at least in terms of the size evolution. Mechanistic insights into protein corona formation on nanoscale antibody aggregates are useful for understanding the unintentional biological impacts of antibody drugs.
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http://dx.doi.org/10.1021/acsami.2c08271DOI Listing
July 2022

Affinity of phenolic compounds for transition metal ions immobilized on cation-exchange columns.

J Chromatogr A 2022 Aug 24;1676:463277. Epub 2022 Jun 24.

Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan. Electronic address:

Immobilized metal ion affinity chromatography (IMAC) is useful in purification of histidine-tagged or histidine-rich proteins and peptides from a variety of hosts. However, phenolic compounds including polyphenols interfere with IMAC due to their high affinities for the transition metals immobilized on the column resins, which hampers the purification of proteins from plant-based host systems. In contrast to extensive knowledge of the mechanism of the interactions between phenolic compounds and transition metal ions in solution, an understanding of the interactions on the columns, where transition metal ions are immobilized on the resins, remains elusive. This study systematically investigated the affinity of phenolic compounds for transition metal ions by varying the number and position of phenolic hydroxyl groups (OH groups) and using different transition metals-Fe(II), Cu(II) and Ni(II)-on various IMACs, in which the columns were fabricated by equilibrating the cation-exchange column with transition metal solutions. It was found that the more OH groups the aromatic compounds have, the higher the affinity for transition metal ions; in particular, methyl gallate and pyrogallol were permanently bound to the IMAC column, which reflected coordinate bond formation with the transition metal ions. Importantly, the phenolic compounds showed no obvious affinity for the Ni(II)-IMAC column, in contrast to the Fe(II)- and Cu(II)-IMAC columns, whereas imidazole and histidine-tagged proteins showed evident binding to the Ni(II)-IMAC column. Ni(II)-IMAC should thus be especially effective in isolating histidine-tagged and histidine-rich species from phenolic compound-containing systems. These results indicate that the affinity between phenolic compounds and transition metal ions on the column is consistent with the results in solution. They also provide a comprehensive view for devising strategies to improve IMAC purification of target proteins and peptides from samples containing phenolic compounds.
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http://dx.doi.org/10.1016/j.chroma.2022.463277DOI Listing
August 2022

Elucidation of the Potential Hair Growth-Promoting Effect of , Its Novel Compound Methylated-Meijicoccene, and C32 Botryococcene on Cultured Hair Follicle Dermal Papilla Cells Using DNA Microarray Gene Expression Analysis.

Biomedicines 2022 May 20;10(5). Epub 2022 May 20.

Research and & Development Center for Tailor-Made QOL Program, University of Tsukuba, Tsukuba City 305-8550, Japan.

A person's quality of life can be adversely affected by hair loss. Microalgae are widely recognized for their abundance and rich functional components. Here, we evaluated the hair growth effect of a green alga, (), in vitro using hair follicle dermal papilla cells (HFDPCs). We isolated two types of cells from -green and orange cells, obtained from two different culture conditions. Microarray and real time-PCR results revealed that both cell types stimulated the expression of several pathways and genes associated with different aspect of the hair follicle cycle. Additionally, we demonstrated ' effect on collagen and keratin synthesis and inflammation reduction. We successfully isolated a novel compound, methylated-meijicoccene (me-meijicoccene), and C32 botryococcene from to validate their promising effects. Our study revealed that treatment with the two compounds had no cytotoxic effect on HFDPCs and significantly enhanced the gene expression levels of hair growth markers at low concentrations. Our study provides the first evidence of the underlying hair growth promoting effect of and its novel compound, me-meijicoccene, and C32 botryococcene.
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http://dx.doi.org/10.3390/biomedicines10051186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138970PMC
May 2022

One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: a real-world prospective study.

Intest Res 2022 Apr 29;20(2):260-268. Epub 2022 Apr 29.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Fukuoka, Japan.

Background/aims: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC.

Methods: Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences.

Results: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment.

Conclusions: One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.
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http://dx.doi.org/10.5217/ir.2021.00124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081999PMC
April 2022

The Compositional Structure of the Small Intestinal Microbial Community via Balloon-Assisted Enteroscopy.

Digestion 2022 8;103(4):308-318. Epub 2022 Apr 8.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Introduction: An association has been found between human-gut microbiota and various diseases (e.g., metabolic disease) by analyzing fecal or colonic microbiota. Despite the importance of the small intestinal microbiota, sampling difficulties prevent its full analysis. We investigated the composition and metagenomic functions of microbiota along the small intestine and compared them with the microbiota from feces and from other gastrointestinal (GI) sites.

Methods: Mucosal samples from the six GI sites (stomach, duodenum, distal jejunum, proximal ileum, terminal ileum, and rectum) were collected under balloon-assisted enteroscopy. Fecal samples were collected from all participants. The microbial structures and metagenomic functions of the small intestinal mucosal microbiota were compared with those from feces and other GI sites using 16S ribosomal RNA gene sequencing.

Results: We analyzed 133 samples from 29 participants. Microbial beta diversity analysis showed that the jejunum and ileum differed significantly from the lower GI tract and the feces (p < 0.001). Jejunal and duodenal microbiotas formed similar clusters. Wide clusters spanning the upper and lower GI tracts were observed with the ileal microbiota, which differed significantly from the jejunal microbiota (p < 0.001). Veillonella and Streptococcus were abundant in the jejunum but less so in the lower GI tract and feces. The metagenomic functions associated with nutrient metabolism differed significantly between the small intestine and the feces.

Conclusions: The fact that the compositional structures of small intestinal microbiota differed from those of fecal and other GI microbiotas reveals that analyzing the small intestinal microbiota is necessary for association studies on metabolic diseases and gut microbiota.
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http://dx.doi.org/10.1159/000524023DOI Listing
July 2022

Characteristics of recurrent cases after conservative therapy in adolescent lumbar spondylolysis.

Sci Rep 2022 03 7;12(1):4019. Epub 2022 Mar 7.

Department of Orthopaedic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Occasionally lumbar spondylolysis in adolescents will recur after conservative treatment. The goal of this study was to retrospectively review the conditions in which recurrence transpired in a subset of adolescent patients diagnosed with acute lumbar spondylolysis. A retrospective survey was conducted in 141 patients who had been treated for spondylolysis and had obtained bone union. Twenty subjects were selected who had recurrent lumbar spondylolysis after returning to sports activity following the initial spondylolysis treatment. There were 18 males and two females with an average age at the time of initial visit of 13.3 years and 14.1 years at the time of recurrence. The average period of initial treatment was 101 days, and the average time to recurrence after healing was 149 days. There were three cases at L3, two cases at L4 and 15 cases at L5. At recurrence, 18 patients had unilateral involvement and two patients presented with bilateral occurrence. Four cases did not achieve bony union. In this study, the recurrence rate was 13.2%. Eighty percent of cases had recurrence within six months after healing. After recurrence, 20% of the cases reached pseudoarthrosis. It is useful to take regular MRI images to detect recurrence within six months after returning to sports.
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http://dx.doi.org/10.1038/s41598-022-07884-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901666PMC
March 2022

Preoperative neutrophil-to-lymphocyte ratio may contribute to the prediction of postoperative infectious complications in patients with acute appendicitis: a retrospective study.

BMC Surg 2022 Mar 3;22(1):78. Epub 2022 Mar 3.

Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare Ichikawa Hospital, 6-1-14 Kounodai, Ichikawa, Chiba, 272-0827, Japan.

Background: Several studies have assessed various clinical variables to identify risk factors for postoperative complications in patients with acute appendicitis. However, few studies have focused on the relationships between systemic inflammatory variables and postoperative complications in patients with acute appendicitis. We investigated the relationships between postoperative complications and systemic inflammatory variables, and assessed the clinical utility of these variables as predictors of postoperative complications in patients with acute appendicitis.

Methods: We retrospectively reviewed 181 patients who underwent immediate appendectomy for acute appendicitis. All postoperative complications were classified as infectious or noninfectious, and we evaluated the relationships between postoperative complications and clinical factors including the preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

Results: In total, 28 patients (15.5%) had postoperative Clavien-Dindo grade II-IV complications; 17 patients (9.4%) and 11 patients (6.1%) were categorized as the infectious and noninfectious complication groups, respectively. The cutoff value of the preoperative neutrophil-to-lymphocyte ratio for all complications was 11.3, and multivariate analysis revealed that the preoperative neutrophil-to-lymphocyte ratio was an independent predictor of any postoperative complication (odds ratio: 4.223, 95% confidence interval: 1.335-13.352; P = 0.014). The cutoff value of the preoperative neutrophil-to-lymphocyte ratio for infectious complications was 11.4, and multivariate analysis revealed that the preoperative neutrophil-to-lymphocyte ratio was an independent predictor of infectious complications (odds ratio: 4.235, 95% confidence interval: 1.137-15.776; P = 0.031).

Conclusions: In patients with acute appendicitis, the preoperative neutrophil-to-lymphocyte ratio may be a useful predictor of all postoperative complications, especially infectious complications.
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http://dx.doi.org/10.1186/s12893-022-01529-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892689PMC
March 2022

[Stoma Site Marking of Colostomy Using Colostomy Simulation 3D-CT-A Case Report].

Gan To Kagaku Ryoho 2021 Dec;48(13):1553-1555

Dept. of Surgery, Secomedic Hospital.

Background And Purpose: Stoma site marking is performed by inspection and palpation of the body surface. In stoma site, it is estimated that transverse colon is epigastric lesion and sigmoid colon is left hypogastric lesion. We try making colostomy simulation(Cs)3D-CT by which stoma site marking is able to be performed considering exact form of colon.

Patient And Method: The patient was 50s man with advanced rectal cancer and unresectable multiple liver metastases. Colonostomy was scheduled for strong rectal stenosis. Standard contrast-enhanced CT scan was performed before operation, and 3D-CT imaging was maked using Workstation Ziostation2(ziosoft, Tokyo, Japan). 3D-CT imaging of abdominal wall was maked by synthesizing 3D-CT imaging of body surface and rectus abdominis muscle. Cs3D-CT is maked by synthesizing CT colonography and 3D-CT imaging of abdominal wall.

Result: The simulation of stoma site marking was performed using Cs3D-CT. Inferior epigastric artery(IEA)was identified, it was to simulate elevated colons and the stoma sites to enable easy elevation of colon through rectus abdominis muscle avoiding injury of IEA. It was possible to measure the distance from navel to stoma site marking on 3D-CT imaging, final stoma site marking was decided by applying the simulation to real stoma site marking. The difficulty of operation was assessed from positional relationship between colon and abdominal wall. It seemed to be relatively easy to elevate sigmoid colon because sigmoid colon was directly under the rectus abdominis muscle. Sigmoidostomy was scheduled considering rectal cancer, and trephine sigmoidostomy with double orifices was performed in fact.

Conclusion: Cs3D-CT was possible to simulate colostomy considering the exact form of colon and positional relationship to abdominal wall and to perform stoma site marking considering the exact form of rectus abdominis muscle and position of IEA. Using Cs3D-CT, it seems to be able to perform optimal stoma site marking which is difficult by conventional method.
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December 2021

High-definition magnetic resonance images on medial elbow injuries in preadolescent Little Leaguers.

J Orthop Sci 2022 Jan 5. Epub 2022 Jan 5.

Department of Orthopaedic Surgery and Sports Medicine, Mito Clinical Education and Training Center, University of Tsukuba Hospital, Mito Kyodo General Hospital, 3-2-7 Miya-Machi, Mito, Ibaraki, 310-0015, Japan.

Background: The incidence of throwing-related elbow injuries is still rising. The study aimed to enhance the pathology of acute medial elbow injuries among young Little Leaguers by examining the medial elbows of symptomatic 9-10 years old Little Leaguers using High-Definition Magnetic Resonance Images (HDMRI), which uses a small-diameter surface coil on the target area, leading to greater image resolution.

Method: We identified Little Leaguers aged 9-10 years old. To minimize the detection of the chronic adaptative changes, players who experienced the medial elbow pain previously and whose HDMRI had not been taken within 4 weeks from the onset of medial elbow pain were excluded. This study considered 21 players, and the mean age was 9.4 ± 0.5 years.

Result: The fragmentation of the medial epicondyle apophysis via HDMRI was found in 15 elbows (71.4%), while the avulsion was seen in three cases. The signal hyperintensity at the medial epicondyle apophysis was observed in 2 cases. Our data showed abnormal changes to the medial epicondyle apophysis and surrounding structures, such as the ulnar collateral ligament (UCL), flexor-pronator tendons or the coronoid process of the ulna. We detected 11 abnormalities on X-ray imaging, while 20 subjects showed some abnormal findings via HDMRI.

Discussion: The current study showed that initial medial elbow injury in Little Leaguers without a history of previous elbow injury could be attributed to multi-structure injury. Over 90% of subjects were injured in the perichondrium, while 71.4% demonstrated a fragmentation of the secondary ossification center, and 14.3% experienced an avulsion of the medial epicondyle apophysis. Because the injuries were not limited to bony structures, HDMRI may be beneficial for the appropriate evaluation of medial elbow pain. The pathology of initial medial elbow injuries in young baseball players may be due to acute trauma instead of repetitive microtrauma.
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http://dx.doi.org/10.1016/j.jos.2021.12.011DOI Listing
January 2022

Crohn's Disease and Early Exposure to Thiopurines are Independent Risk Factors for Mosaic Chromosomal Alterations in Patients with Inflammatory Bowel Diseases.

J Crohns Colitis 2022 May;16(4):643-655

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background And Aims: Mosaic chromosomal alterations [mCAs] increase the risk for haematopoietic malignancies and may be risk factors for several other diseases. Inflammatory bowel diseases [IBDs], including Crohn's disease [CD] and ulcerative colitis [UC], are associated with mCAs, and patients may be at risk for haematopoietic malignancy development and/or modification of IBD phenotypes. In the present study, we screened patients with IBD for the presence of mCAs and explored the possible pathophysiological and genetic risk factors for mCAs.

Methods: We analysed mCAs in peripheral blood from 3339 patients with IBD and investigated the clinical and genetic risk factors for mCAs.

Results: CD and exposure to thiopurines before the age of 20 years were identified as novel independent risk factors for mCAs [odds ratio = 2.15 and 5.68, p = 1.17e-2 and 1.60e-3, respectively]. In contrast, there were no significant associations of disease duration, anti-tumour necrosis factor alpha antibodies, or other clinical factors with mCAs. Gene ontology enrichment analysis revealed that genes specifically located in the mCAs in patients with CD were significantly associated with factors related to mucosal immune responses. A genome-wide association study revealed that ERBIN, CD96, and AC068672.2 were significantly associated with mCAs in patients with CD [p = 1.56e-8, 1.65e-8, and 4.92e-8, respectively].

Conclusions: The difference in mCAs between patients with CD and UC supports the higher incidence of haematopoietic malignancies in CD. Caution should be exercised when using thiopurines in young patients with IBD, particularly CD, in light of possible chromosomal alterations.
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http://dx.doi.org/10.1093/ecco-jcc/jjab199DOI Listing
May 2022

Gastric microbiota in patients with Helicobacter pylori-negative gastric MALT lymphoma.

Medicine (Baltimore) 2021 Sep;100(38):e27287

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Abstract: To investigate the mucosal microbiota in the stomach of patients with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma by means of metagenomic analysis.Although some gastric MALT lymphomas are associated with the presence of H. pylori, other gastric MALT lymphomas occur independently of H. pylori infection. The pathogenesis of H. pylori-negative MALT lymphoma remains unclear.Mucosal biopsy specimens were collected from the gastric body from 33 MALT lymphoma patients with gastric lesions, including both H. pylori-infection naïve patients and posteradication patients, as well as 27 control participants without H. pylori infection or cancer. Subsequently, the samples were subjected to 16S rRNA gene sequencing. Quantitative insights into microbial ecology, linear discriminant analysis effect size, and phylogenetic investigation of communities by reconstruction of unobserved states softwares were used to analyze the participants' microbiota.H. pylori-negative MALT lymphoma patients had significantly lower alpha diversity (P = .04), compared with control participants. Significant differences were evident in the microbial composition (P = .04), as determined by comparison of beta diversity between the 2 groups. Taxonomic composition analysis indicated that the genera Burkholderia and Sphingomonas were significantly more abundant in MALT lymphoma patients, while the genera Prevotella and Veillonella were less abundant. Functional microbiota prediction showed that the predicted gene pathways "replication and repair," "translation," and "nucleotide metabolism" were downregulated in MALT lymphoma patients.H. pylori-negative MALT lymphoma patients exhibited altered gastric mucosal microbial compositions, suggesting that altered microbiota might be involved in the pathogenesis of H. pylori-negative MALT lymphoma.
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http://dx.doi.org/10.1097/MD.0000000000027287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462607PMC
September 2021

Ustekinumab Improves Active Crohn's Disease by Suppressing the T Helper 17 Pathway.

Digestion 2021 22;102(6):946-955. Epub 2021 Jul 22.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Ustekinumab (UST), an antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, is effective in treating Crohn's disease (CD). To clarify the mechanism of UST, we investigated T-cell differentiation in CD patients treated with UST.

Methods: Twenty-seven patients with active CD were enrolled in this study. Seventeen patients were treated with UST, and 10 patients were treated with anti-tumor necrosis factor (TNF)-alpha therapy. The changes in the proportions of T-cell subsets after these therapies were analyzed by flow cytometry. Comprehensive gene expression changes in the colonic mucosa were also evaluated.

Results: The frequency of T helper (Th) 17 cells was significantly decreased in the peripheral blood of patients with active CD after UST therapy. Anti-TNF therapy had a minimal effect on Th17 cells but increased the proportion of regulatory T cells. Enrichment analysis showed the expression of genes involved in the Th17 differentiation pathway was downregulated in the colonic mucosa after UST but not anti-TNF therapy. There were no common differentially expressed genes between CD patients treated with UST and anti-TNF therapy, suggesting a clear difference in their mechanism of action.

Conclusion: In patients with active CD, UST therapy suppressed Th17 cell differentiation both in the peripheral blood and colonic tissues.
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http://dx.doi.org/10.1159/000518103DOI Listing
November 2021

Preoperative Neutrophil-to-Lymphocyte Ratio may Predict Postoperative Pneumonia in Stage I-III Gastric Cancer Patients After Curative Gastrectomy: A Retrospective Study.

World J Surg 2021 11 31;45(11):3359-3369. Epub 2021 Jul 31.

Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare Ichikawa Hospital, 6-1-14 Kounodai, Ichikawa, Chiba, 272-0827, Japan.

Background: Several studies have demonstrated that diverse systemic inflammatory-based prognostic parameters predict a poor prognosis in patients with gastric cancer. However, few studies have focused on the relationships between postoperative complications and systemic inflammatory-based prognostic parameters after curative gastrectomy. We investigated the relationships between postoperative complications and these parameters and assessed the clinical utility of the parameters as predictors of postoperative complications in patients with stage I-III gastric cancer.

Methods: We retrospectively reviewed 300 patients who underwent curative gastrectomy for stage I-III gastric cancer. All postoperative complications were classified as infectious or noninfectious. We evaluated the relationships between postoperative complications and clinical factors, including systemic inflammatory-based prognostic parameters.

Results: In total, 101 patients (33.7%) had postoperative Clavien-Dindo grade II-IV complications, and 54 (18.0%) patients developed infectious complications including pancreatic fistula, pneumonia, anastomotic leak, intra-abdominal abscess, and cholecystitis. The relationships between postoperative complications and systemic inflammatory-based prognostic parameters were evaluated by the areas under the receiver operating characteristic curves. Postoperative pneumonia was identified as the most sensitive complication to the systemic inflammatory-based prognostic parameters. Multivariate analysis revealed that preoperative neutrophil-to-lymphocyte ratio (odds ratio, 14.621; 95% confidence interval, 1.160-184.348; p = 0.038) was an independent predictor of pneumonia.

Conclusions: Preoperative neutrophil-to-lymphocyte ratio may be a useful predictor of postoperative pneumonia in patients with stage I-III gastric cancer after curative gastrectomy.
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http://dx.doi.org/10.1007/s00268-021-06264-4DOI Listing
November 2021

Risk of Rebleeding in Patients with Small Bowel Vascular Lesions.

Intern Med 2021 Dec 12;60(23):3663-3669. Epub 2021 Jun 12.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan.

Objective With recent advances in endoscopic modalities, small bowel vascular lesions (SBVLs) are often now detected in patients with gastrointestinal bleeding. Given the high invasiveness of endoscopic treatment, it is important to select patients at high risk for bleeding. To assess the risk of rebleeding in patients with SBVLs as a systemic disease rather than a gastrointestinal disease in relation to their general health. Methods We retrospectively analyzed the clinical data of 55 patients with SBVLs among patients with obscure gastrointestinal bleeding. The possible association between the clinical findings and the updated Charlson comorbidity index with rebleeding was evaluated. Results Gastrointestinal rebleeding occurred in 20 patients (36.4%) during the follow-up period. The presence of multiple comorbidities as indicated by an updated Charlson comorbidity index of ≥4 was a risk factor for rebleeding (hazard ratio, 3.64; p=0.004). Other risk factors were arteriosclerosis of the superior mesenteric artery and multiple SBVLs. Endoscopic hemostasis and the discontinuation of antithrombotic medications were not significantly associated with rebleeding. Patients with a high updated Charlson comorbidity index had a high risk of death of causes other than gastrointestinal rebleeding. Conclusion Gastrointestinal rebleeding is not a rare condition among patients with SBVLs. Patients with poor general health may therefore have a higher risk of rebleeding.
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http://dx.doi.org/10.2169/internalmedicine.6341-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710388PMC
December 2021

Features of sacral alar fatigue fractures in adolescent athletes with overuse.

Sci Rep 2021 04 19;11(1):8420. Epub 2021 Apr 19.

Department of Orthopaedic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Three types of sacral alar fatigue fractures are elderly, postnatal, and sport-related. They are most prevalent in athletes during adulthood; there are few reports of sacral alar fatigue fractures in young athletes. The purpose of this study was to analyze sacral alar fatigue fractures in adolescent athletes. Of the 920 patients hospitalized with low back pain, 13 were diagnosed with sacral alar fatigue fractures with magnetic resonance imaging (MRI) abnormalities. We investigated age, sex, sports discipline, span from symptom onset to consultation, laterality, complication with spondylolysis, computed tomography (CT) findings, and treatment span. The average age was 14.5 years old (8-men and 5-women). The most frequent discipline was basketball. The span to consultation was 13.2 days. The number of right-side cases was 9. Seven cases were complicated by bilateral spondylolysis. MRI abnormalities were observed in all the cases. Only two patients showed abnormal findings on CT. Averagely 67 days after treatment, participants returned to their sports. Sacral alar fatigue fractures suggest that the span from onset to consultation is short. Fracture lines are often unclear on CT, and MRI is useful for diagnosis. More than half of the cases in this study were complicated by lumbar spondylolysis.
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http://dx.doi.org/10.1038/s41598-021-87752-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055686PMC
April 2021

[Investigation for Arc of Riolan-Conserving High Ligation Using Simulation CT Colonography in Preoperative Colorectal Cancer].

Gan To Kagaku Ryoho 2021 Mar;48(3):428-430

Dept. of Surgery, International University of Health and Welfare Ichikawa Hospital.

Background And Purpose: Simulation computed tomography colonography(sCTC), which combines CTC and 3-dimensional vascular imaging, is popular for the surgery of colorectal cancer. We experience anomaly, called arc of Riolan(aR), rarely but its definition and details are unclear. Using sCTC, we identified aR and investigated the simulation of aR-conserving high ligation.

Patient And Method: The patients were 3 cases of sigmoid colorectal cancer with aR in 369 patients who underwent sCTC before colorectal cancer surgery. We identified the running morphology of aR. And we classified Griffiths' point as presence(P)and absence(A). Narrow or mesh-shaped artery which were ischemic risk factors of intestinal tract was P groups and normal artery was A groups in the marginal artery of splenic flexure. We simulated aR-conserving lymph node dissection using sCTC.

Result: Case 1. The patient was 60-year-old man with rectal cancer, cT4aN1M0, Stage Ⅲa. The running morphology of aR was between the left branch of middle colic artery(MCA lt)and LCA. Griffiths point: P. Surgical simulation was D3 lymph node dissection with preservation of aR and high ligation of IMA. Pathological findings was pT3N1M0, Stage Ⅲa. Case 2. The patient was 65-year-old woman with sigmoid colon cancer, cT3N2M0, Stage Ⅲb. The running morphology of aR was between MCA lt and IMA. Griffiths point: P. Surgical simulation was D3 lymph node dissection with preservation of aR and high ligation of IMA. Pathological findings was pT3N2M0, Stage Ⅲb. Case 3. The patient was 75-year-old woman with sigmoid colon cancer, cT1bN0M0, Stage Ⅰ. The running morphology of aR was between first jejunal artery and IMA. Griffiths point: A. Surgical simulation was D3 lymph node dissection with preservation of aR and high ligation of IMA. Pathological findings was pT1bN0M0, Stage Ⅲb.

Conclusion: Using sCTC, we could identify the various running morphology of aR and simulate aR-conserving lymph node dissection in high ligation.
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March 2021

Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS.

Sci Rep 2021 03 23;11(1):6643. Epub 2021 Mar 23.

Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Koto, Tokyo, 135-0064, Japan.

Liquid droplets of aggregation-prone proteins, which become hydrogels or form amyloid fibrils, are a potential target for drug discovery. In this study, we proposed an experiment-guided protocol for characterizing the design grammar of peptides that can regulate droplet formation and aggregation. The protocol essentially involves investigation of 19 amino acid additives and polymerization of the identified amino acids. As a proof of concept, we applied this protocol to fused in sarcoma (FUS). First, we evaluated 19 amino acid additives for an FUS solution and identified Arg and Tyr as suppressors of droplet formation. Molecular dynamics simulations suggested that the Arg additive interacts with specific residues of FUS, thereby inhibiting the cation-π and electrostatic interactions between the FUS molecules. Second, we observed that Arg polymers promote FUS droplet formation, unlike Arg monomers, by bridging the FUS molecules. Third, we found that the Arg additive suppressed solid aggregate formation of FUS, while Arg polymer enhanced it. Finally, we observed that amyloid-forming peptides induced the conversion of FUS droplets to solid aggregates of FUS. The developed protocol could be used for the primary design of peptides controlling liquid droplets and aggregates of proteins.
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http://dx.doi.org/10.1038/s41598-021-86098-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988016PMC
March 2021

The solubility of N-acetyl amino acid amides in organic acid and alcohol solutions: Mechanistic insight into structural protein solubilization.

Int J Biol Macromol 2021 May 23;178:607-615. Epub 2021 Feb 23.

Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Koto, Tokyo 135-0064, Japan.

Structural proteins such as spider silk and silkworm silk are generally poorly soluble in aqueous and organic solutions, making them difficult to manipulate in manufacturing processes. Although some organic acids and alcohols, such as formic acid and hexafluoroisopropanol (HFIP), effectively solubilize poorly soluble proteins, little is known about their protein solubilization mechanism. In this study, the solubility of N-acetyl amino acid amide compounds in organic solvents-formic acid, acetic acid, HFIP and isopropanol-was measured to clarify the protein solubilization mechanism at the amino acid residue level. On the basis of thermodynamic analyses of the solubility in terms of the transfer free energy (from water to organic solvents), every organic solvent was found to be effective in thermodynamically stabilizing hydrophobic amino acid side chains in the liquid phase. Formic acid and HFIP were comparably effective in the stabilization of the polypeptide backbone, whereas acetic acid and isopropanol were ineffective. Therefore, the significant solubilizing effect of formic acid and HFIP on the structural proteins was attributed to their favorable interactions with hydrophobic amino acid side chains and with the polypeptide backbone of the proteins. The present findings are useful for the optimization of protein manipulation and amino acid sequence design.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.141DOI Listing
May 2021

Union evaluation of lumbar spondylolysis using MRI and CT in adolescents treated conservatively.

J Orthop Sci 2022 Mar 15;27(2):317-322. Epub 2021 Feb 15.

Department of Orthopaedic Surgery, Faculty of Medicine, University of Tsukuba, Tuskuba, Ibaraki, Japan.

Background: This study evaluated the union rate of acute lumbar spondylolysis in patients treated conservatively, according to the protocol.

Methods: The subjects included high school students and younger patients who were diagnosed with lumbar spondylolysis presenting bone marrow edema. We investigated the union rate, the period until union, unilateral or bilateral, vertebral level, laterality (right or left), and pathological stage at the first visit. Some unilateral cases included bilateral spondylolysis with contralateral pseudarthrotic lesion; therefore, the union rate of the "true" unilateral case in which the contralateral side was normal was calculated. We excluded multi-level lesions.

Results: With conservative treatment for lumbar spondylolysis of 189 lesions in 142 cases, 144 healed and 45 were considered as nonunion. The average treatment period until union was 106 days. The union of "true" unilateral cases in which the contralateral side was normal was noted in 68/71 lesions, but that of bilateral cases was noted in 71/94 lesions. The union in L3, L4, and L5 vertebrae was noted in 15/17, 40/49, and 89/123 lesions, respectively. The union was observed in 63/87 on the right and 86/102 on the left. The union was noted in the pre-lysis, early, and progressive stages in 36/39, 81/97, and 27/53 lesions, respectively. Furthermore, the union was noted in stages 0, 1a, 1b, 1c, and 2 in 13/15, 47/52, 30/36, 34/42, and 20/44 lesions, respectively.

Conclusion: Accurate union evaluation using CT and MRI showed a union rate of 76% with conservative treatment for spondylolysis. The union rate of the "true" unilateral cases in which the contralateral side was normal was 96%, which was significantly higher than that of the bilateral cases. Moreover, the union rate of lesions in the axial progressive stage and sagittal stage 2 was significantly lower than that of lesions in other stages.

Study Design: clinical retrospective study.
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http://dx.doi.org/10.1016/j.jos.2021.01.002DOI Listing
March 2022

Successful treatment by doravirine with cobicistat-boosted darunavir for end-stage renal failure under chronic haemodialysis.

J Antimicrob Chemother 2021 04;76(5):1370-1372

Department of Pharmacy, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.

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http://dx.doi.org/10.1093/jac/dkab001DOI Listing
April 2021

Interactions between Amino Acids and Zirconia Modified with Ethylenediaminetetra(methylenephosphonic acid): Mechanistic Insights into the Selective Binding of Antibodies.

Langmuir 2021 02 21;37(4):1605-1612. Epub 2021 Jan 21.

NGK Spark Plug-AIST Healthcare Materials Cooperative Research Laboratory, Anagahora, Shimo-Shidami, Moriyama-ku, Nagoya, Aichi 463-8560, Japan.

Zirconia modified with ethylenediaminetetra(methylenephosphonic acid) (EDTMP) has an affinity for antibodies, including immunoglobulin G (IgG) and immunoglobulin M (IgM). However, little is known about the mechanism underlying antibody selectivity. In this study, we examined the interactions of EDTMP-modified zirconia with proteinogenic amino acids using chromatographic and batch methods to gain mechanistic insights into antibody selectivity at the amino acid level. We demonstrated that EDTMP-modified zirconia has an affinity for amino acids with a positively charged side chain, especially lysine. Similar trends were observed for oligopeptides. This affinity was reduced by the addition of sodium phosphate or sodium polyphosphates. Thus, the antibody selectivity of EDTMP-modified zirconia is primarily ascribable to electrostatic attractions between the EDTMP moieties of the zirconia surfaces and the constant region of antibodies that are rich in lysine residues. Consistent with this, the human IgG antibody has a higher adsorption ability onto EDTMP-modified zirconia than the rabbit IgG antibody, which has fewer lysine residues in the constant region. These findings are useful not only for improving antibody purification but also for developing new applications, including purification of proteins tagged with positively charged amino acid residues.
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http://dx.doi.org/10.1021/acs.langmuir.0c03471DOI Listing
February 2021

Direct reduction and repair of spondylolysis with grade 1 slip using the smiley face rod: a case report.

J Rural Med 2021 Jan 5;16(1):56-61. Epub 2021 Jan 5.

Department of Orthopedics Surgery, Faculty of Medicine, University of Tsukuba, Japan.

Lumbar spondylolysis, caused by stress fracture of the pars interarticularis may lead to a bony defect or spondylolisthesis. In adolescents, its surgical treatment employs the smiley face rod method for direct reduction of pseudoarthrotic spondylolysis and spondylolisthesis. Clinical outcomes of this treatment have been occasionally described; however, implant removal has not been discussed previously. We present a patient with lumbar spondylolysis with grade 1 slip at the 5th lumbar vertebra (L5) per the Meyerding classification. A 14-year-old boy presented with chronic severe lower back pain. Since conservative therapy did not resolve pain or enable resuming sports activities, the smiley face rod repair was performed 7 months after the initial treatment. Anterior slippage of the L5 was surgically reduced. The patient wore a brace for 3 months postoperatively, and partial bone fusion was noted 6 months postoperatively. He resumed his sports activity 8 months postoperatively, and absolute bone fusion was confirmed 18 months postoperatively. Implant removal was performed 3 years postoperatively. Grade 1 slip was corrected with absolute bone fusion, and long-term follow-up revealed good results in terms of healing and rehabilitation. Smiley face rod method that allows for implant removal after bone fusion is suitable for adolescents.
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http://dx.doi.org/10.2185/jrm.2020-039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788300PMC
January 2021

Factors associated with failure of bony union after conservative treatment of acute cases of unilateral lumbar spondylolysis.

BMC Musculoskelet Disord 2021 Jan 13;22(1):75. Epub 2021 Jan 13.

Department of Orthopaedic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Background: If bone union is expected, conservative treatment is generally selected for lumbar spondylolysis. However, sometimes conservative treatments are unsuccessful. We sought to determine the factors associated with failure of bony union in acute unilateral lumbar spondylolysis with bone marrow edema including contralateral pseudarthrosis.

Methods: This study targeted unilateral lumbar spondylolysis treated conservatively in high school or younger students. Conservative therapy was continued until the bone marrow edema disappeared on MRI and bone union was investigated by CT. We conducted a univariate analysis of sex, age, pathological stage, lesion level complicating the contralateral bone defect, lesion level, and intercurrent spina bifida occulta, and variables with p < 0.1 were considered in a logistic regression analysis. An item with p < 0.05 was defined as a factor associated with failure of bony union.

Results: We found 92 cases of unilateral spondylolysis with bone marrow edema and 66 cases were successfully treated conservatively. Failure of bony union in unilateral lumbar spondylolysis with bone marrow edema was associated with progressive pathological stage (p = 0.004), contralateral pseudarthrosis (p < 0.001), and L5 lesion level (p = 0.002). The odds ratio was 20.0 (95% CI 3.0-193.9) for progressive pathological stage, 78.8 (95% CI 13-846) for contralateral pseudarthrosis, and 175 (95% CI 8.5-8192) for L5 lesion level.

Conclusions: Conservative therapy aiming at bony union is contraindicated in cases of acute unilateral spondylolysis when the pathological stage is progressive, the lesion level is L5, or there is contralateral pseudarthrotic spondylolysis.
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http://dx.doi.org/10.1186/s12891-020-03940-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807717PMC
January 2021

Recurrent hemarthrosis after total knee arthroplasty in rheumatoid arthritis successfully treated with selective embolization: A case report.

SAGE Open Med Case Rep 2020 10;8:2050313X20964116. Epub 2020 Oct 10.

Department of Orthopaedic Surgery and Sports Medicine, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, University of Tsukuba, Mito, Japan.

Recurrent hemarthrosis after total knee arthroplasty is a rare complication. This usually occurs in osteoarthritis, but is relatively rare in rheumatoid arthritis. This is a report of recurrent hemarthrosis after total knee arthroplasty in a rheumatoid arthritis patient. An 85-year-old woman with rheumatoid arthritis had received total knee arthroplasty without acute complications. At 6 months after surgery, the first hemarthrosis occurred and an initial conservative treatment failed. Contrast computed tomography showed prominent synovial enhancement in the superior lateral suprapatellar pouch. Selective catheterization revealed an abnormal hyperemic blush supplied from the branches of the superior lateral genicular artery. After embolization with N-butyl-2-cyanoacrylate, abnormal staining of the synovium diminished and knee swelling and pain disappeared without complications. Selective embolization is favorable for successful treatment of recurrent hemarthrosis after total knee arthroplasty in patients with rheumatoid arthritis.
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http://dx.doi.org/10.1177/2050313X20964116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550959PMC
October 2020

Characteristics of adolescent lumbar spondylolysis with acute unilateral fatigue fracture and contralateral pseudoarthrosis.

J Rural Med 2020 Oct 1;15(4):170-177. Epub 2020 Oct 1.

Department of Orthopaedic Surgery and Sports Medicine, Tsukuba University Hospital Mito Clinical Education and Training Center/Mito Kyodo General Hospital, Japan.

This study aimed to examine the characteristics of lumbar spondylolysis with acute lumbar spondylolysis on one side and pseudoarthrotic spondylolysis on the other, relative to acute lumbar spondylolysis on one side only. Short-tau inversion recovery images obtained through magnetic resonance imaging were used to diagnose 58 patients with acute lumbar spondylolysis with bone marrow edema on one side only. A total of 20 patients who had pars defects on the contralateral side (terminal-stage pseudoarthrotic spondylolysis) were included in the contralateral pseudoarthrosis group (P group). The remaining 38 patients with normal images for the contralateral pars interarticularis were included in the unilateral lesion group, in which the contralateral side was normal (U group). We investigated the union rate, age, sex, lesion laterality, vertebral level, pathological stage, and existing spina bifida occulta in both groups. The P group was characterized by a higher proportion of right-side cases, L5 lesions, more progressed pathological stage, and spina bifida occulta and a significantly lower union rate than the U group. The union rate in patients with lumbar spondylolysis with acute lumbar spondylolysis on one side and pseudoarthrotic spondylolysis on the opposite side was only 15%. We should inform patients with acute unilateral spondylolysis lesions and contralateral pseudoarthrosis about this poor union rate and urge them to choose their therapy accordingly.
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http://dx.doi.org/10.2185/jrm.2020-026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530601PMC
October 2020

Positional anterior sternoclavicular joint dislocation in the acceleration phase of throwing: a case report.

JSES Int 2020 Sep 6;4(3):532-535. Epub 2020 May 6.

Department of Orthopaedic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Positional anterior sternoclavicular joint (SCJ) dislocation is relatively rare and needs careful treatment. We report our course of treatment and tips for surgery in a case. The patient was a 16-year-old male outfield baseball player. Three years ago, he had 3 recurrent episodes of right shoulder dislocation. During these injuries, there were forward dislocations of the proximal right clavicle edge accompanied by a creaking sound during the throw acceleration period. Thereafter, the anterior dislocation of the SCJ occurred during the acceleration phase of throwing, and the SCJ naturally repositioned on the shoulder resting position. This situation lingered and he often felt shoulder apprehension during throws, so he opted for surgical treatment just 1 month after the first injury. We performed a modified version of the figure-of-8 technique reported by Wang et al, using the ipsilateral palmaris longus (PL) tendon. The bilateral edge of the PL was attached to a Krackow suture and passed through the bone tunnels opened at the proximal clavicle and proximal sternum so that it became a figure of 8 on the anterior of the SCJ. The stability of the SCJ was confirmed after the surgery.
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http://dx.doi.org/10.1016/j.jseint.2020.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479031PMC
September 2020

Quantitative analysis of the effect of reabsorption on the Raman spectroscopy of distinct (, ) carbon nanotubes.

Anal Methods 2020 05;12(18):2376-2384

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

We quantitatively analyze the effect of reabsorption on the Raman spectroscopy of (10, 3) and (8, 3) single-chirality single-wall carbon nanotube (SWCNT) solutions by varying the detection depth in confocal micro-Raman measurements and SWCNT concentration the in sample solution. The increase of the detection depth and concentration of SWCNTs enhances the reabsorption effect and decreases the intensities of the Raman features. More importantly, reabsorption exhibits different effects on different Raman features such as the radial breathing mode (RBM) and G+ band, strongly depending on the resonance degree of the scattered light energy and the interband transition of SWCNTs. When (10, 3) SWCNTs are excited with a 633 nm laser, the scattered light from RBM has stronger resonance with the interband transition of the SWCNTs than that from the G+ band, leading to a faster reduction in the RBM intensity and a lower intensity ratio of RBM to the G+ band. In contrast, when (8, 3) SWCNTs are excited with a 633 nm laser, reabsorption has the same effect on the RBM and G+ band intensities and thus maintains a constant intensity ratio of RBM to the G+ band. Furthermore, we precisely establish a quantitative relationship of the intensities of the Raman features such as RBM, the G+ band and their intensity ratio as a function of the focal depth and SWCNT concentration by theoretical calculations and numerical simulation, which reproduces the experimental results well. These results are very useful in the precise analysis of the Raman spectroscopy of SWCNTs and thus their applications in molecular detection and imaging.
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http://dx.doi.org/10.1039/d0ay00356eDOI Listing
May 2020

Adding Thiopurine After Loss of Response to Infliximab Versus Early Combination in Treating Crohn's Disease: A Retrospective Study.

Dig Dis Sci 2021 09 13;66(9):3124-3131. Epub 2020 Sep 13.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Background: Although combining thiopurine with infliximab (IFX) is considered to improve the clinical efficacy of IFX when treating Crohn's disease (CD), it also increases the risk of adverse events (AEs). We compared the efficacy and safety of delayed thiopurine addition after loss of response (LOR) to IFX with the efficacy and safety of an earlier combination of thiopurine and IFX.

Methods: This retrospective study analyzed patients with CD who started IFX as a first-line biologic at Kyushu University Hospital between June 2002 and July 2018. Patients were assigned to either the early-combination (EC) group, who started IFX and thiopurine simultaneously, or the late-combination (LC) group, who were treated with IFX alone until they developed LOR. We compared the cumulative IFX continuation rates and AE incidence between the two groups.

Results: One hundred seventy-six patients were enrolled in this study; 49 were enrolled in the EC group, and 127 were enrolled in the LC group. Disease activity at baseline did not significantly differ between the groups, nor did the cumulative IFX continuation rates differ between the groups (P = 0.30); however, the AE rate was significantly higher in the EC group than in the LC group (38.7% vs. 21.2%; P = 0.02). The severe AE rate was also higher in the EC group than in the LC group (18.3% vs 3.1%; P = 0.001).

Conclusion: Considering the risk-benefit balance, delayed addition of thiopurine after LOR to IFX might be an alternative strategy when using IFX to treat CD.
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http://dx.doi.org/10.1007/s10620-020-06600-zDOI Listing
September 2021

An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn's Disease in Japanese Populations.

Sci Rep 2020 06 24;10(1):10236. Epub 2020 Jun 24.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Expression quantitative trait locus (eQTL) analyses have enabled us to predict the function of disease susceptibility SNPs. However, eQTL for the effector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn's disease (CD), are not yet available. Thus, we conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n = 20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confirmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed significant correlation with tenascin-XA (TNXA) expression were significantly associated with CD in GWAS. By TWAS, TNFSF15 (FDR = 1.35e-13) in whole blood, ERV3-1 (FDR = 2.18e-2) in lymphocytes, and ZNF713 (FDR = 3.04e-2) in the sigmoid colon was significantly associated with CD. By conducting integration analyses using GWAS and eQTL data, we confirmed multiple gene transcripts are involved in the development of CD.
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http://dx.doi.org/10.1038/s41598-020-66951-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314801PMC
June 2020

A Novel Parameter Identified Using Indocyanine Green Fluorescence Angiography may Contribute to Predicting Anastomotic Leakage in Gastric Cancer Surgery.

World J Surg 2020 08;44(8):2699-2708

Department of Surgery, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara, Chiba, 299-0111, Japan.

Background: Anastomotic leak is one of the most serious postoperative complications, and intraoperative adequate perfusion plays a key role in preventing its development in gastric cancer surgery. This study aimed to investigate the relationships between anastomotic leak and the parameters defined by an assessment of intraoperative anastomotic perfusion using a near-infrared indocyanine green (ICG) fluorescence system and to evaluate the usefulness of this ICG fluorescence assessment in gastric cancer surgery.

Methods: We retrospectively reviewed data of 100 patients who underwent gastric cancer surgery. In a visual assessment based on fluorescence intensity, we classified ICG fluorescence image patterns as homogeneous, heterogeneous, or faint. In a chronological assessment, the first or second time point of ICG fluorescence appearance on one or the other side of the anastomosis was defined as FT or ST, respectively. The time difference in ICG fluorescence appearance between FT and ST was defined as TD. The relationships between anastomotic leak and the evaluated clinical factors, including the parameters identified by the ICG fluorescence assessment, were evaluated using univariate or multivariate analysis.

Results: Although no signs of leak were found by surgeons' subjective judgments, four patients developed postoperative anastomotic leak of Clavien-Dindo grade III or IV. Multivariate analysis revealed that TD was an independent predictor of anastomotic leak (odds ratio 35.361, 95% confidence interval 1.489-839.923, p = 0.027).

Conclusions: A novel parameter identified using near-infrared ICG fluorescence assessment may be useful to predict anastomotic leak in gastric cancer surgery.

Trial Registration: UMIN Clinical Trials Registry: #UMIN000030747 ( https://www.umin.ac.jp/ctr/index.htm ).
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http://dx.doi.org/10.1007/s00268-020-05488-0DOI Listing
August 2020
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