Existence of a Neuropathic Pain Component in Patients with Osteoarthritis of the Knee

∙ The authors have no financial conflicts of interest. © Copyright: Yonsei University College of Medicine 2012 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

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

Impact of Anti-TNFα Treatment on the Humoral Response to the BNT162b2 mRNA COVID-19 Vaccine in Pediatric Inflammatory Bowel Disease Patients

The efficacy of the COVID-19 mRNA vaccine, including the third vaccination in pediatric inflammatory bowel disease (PIBD) patients is not fully understood. This study aimed to evaluate the humoral immunogenicity of the BNT162b2 vaccine and the changes in durability until 20–28 weeks after the initial vaccine series in PIBD patients on immunosuppressive drugs. The safety of the initial vaccine series and the booster effect of the third vaccination were also evaluated. A single-center, prospective cohort study was conducted, and 63 participants (anti-TNFα: 11; non-anti-TNFα: 31; 5-ASA: 21), with a mean age of 15.2 (range 9.6–17.9) years, were enrolled. All PIBD patients were seroconverted, with no serious short-term AEs. PIBD patients on anti-TNFα had significantly lower antibody titers than those on other medications at all measurement points. Furthermore, antibody titers waned over time with anti-TNFα and were significantly lower at 20–28 weeks than at 3–9 weeks after a two-vaccine series. In all 10 patients (anti-TNFα: 5; non-anti-TNFα including 5-ASA: 5), the third vaccination led to antibody concentrations significantly higher than those at the same time point after the second vaccination. PIBD patients on anti-TNFα need to remain vigilant about COVID-19 even after two vaccinations, and a third vaccination may be considered

A Pediatric Case of Inverted Meckel’s Diverticulum Presenting with Cyclic Vomiting-like Symptoms: A Case Report and Literature Review

Asymptomatic Meckel’s diverticulum cases are not uncommon, leading to diagnostic difficulties in cases of atypical presentations with only gastrointestinal symptoms other than bloody stool. A nine-year-old boy diagnosed as having cyclic vomiting because of recurrent abdominal pain and vomiting for 6 months was referred to our institute and hospitalized due to worsening symptoms. After admission, abdominal ultrasonography showed the multiple concentric ring sign and a pseudokidney sign at the lower ileum, leading to the diagnosis of ileo-ileal intussusception, but the gastrointestinal symptoms and ultrasonic findings disappeared spontaneously. Transanal, double-balloon, intestinal endoscopy demonstrated a pedunculated polyp-like structure, and surgical resection was performed. An inverted diverticulum was found in the resected intestinal lumen, and ectopic gastric mucosa was identified histologically, leading to the diagnosis of inverted Meckel’s diverticulum. In pediatric cases involving periodic attacks of vomiting and abdominal pain, unnecessary emergent surgery could be avoided by cautious imaging evaluation and consideration of ileo-ileal intussusception with advanced lesions of an inverted Meckel’s diverticulum as a differential diagnosis, without facilely diagnosing cyclic vomiting. In addition, previous reports of inverted Meckel’s diverticulum were reviewed, and the results were compared between adult and pediatric groups in each category

An Isolated Intestinal Juvenile Polyp Diagnosed by Abdominal Ultrasonography and Resected by Double-Balloon Endoscopy: A Case Report and Literature Review

Juvenile polyps, typically localized in the rectum and sigmoid colon, are a common cause of pediatric bloody stool. An isolated small intestinal juvenile polyp is uncommon and generally difficult to diagnose. The first case of an isolated juvenile polyp diagnosed by abdominal ultrasonography before acute abdomen had developed and resected by double-balloon endoscopy is presented along with a review of previous reports including this case. A two-year-old Japanese boy was referred to our institute for further evaluation of anemia persisting from one year of age. Laboratory findings showed mild iron deficiency anemia and elevated fecal human hemoglobin (Hb) and fecal calprotectin values. Upper and lower endoscopic findings showed no abnormalities. Because the abdominal ultrasonography performed one year later demonstrated a 15 mm jejunal polyp, combined with a similar finding on small intestinal capsule endoscopy, this was diagnosed as an isolated lesion. The lesion was resected by cautery with double-balloon endoscopy and diagnosed as a juvenile polyp pathologically. All clinical symptoms disappeared, and all laboratory data improved after treatment, without recurrence for more than one year after the procedure. Abdominal ultrasonographic screening and the fecal calprotectin value led to the diagnosis and non-surgical invasive treatment of an isolated small intestinal juvenile polyp

An Isolated Intestinal Juvenile Polyp Diagnosed by Abdominal Ultrasonography and Resected by Double-Balloon Endoscopy: A Case Report and Literature Review

Juvenile polyps, typically localized in the rectum and sigmoid colon, are a common cause of pediatric bloody stool. An isolated small intestinal juvenile polyp is uncommon and generally difficult to diagnose. The first case of an isolated juvenile polyp diagnosed by abdominal ultrasonography before acute abdomen had developed and resected by double-balloon endoscopy is presented along with a review of previous reports including this case. A two-year-old Japanese boy was referred to our institute for further evaluation of anemia persisting from one year of age. Laboratory findings showed mild iron deficiency anemia and elevated fecal human hemoglobin (Hb) and fecal calprotectin values. Upper and lower endoscopic findings showed no abnormalities. Because the abdominal ultrasonography performed one year later demonstrated a 15 mm jejunal polyp, combined with a similar finding on small intestinal capsule endoscopy, this was diagnosed as an isolated lesion. The lesion was resected by cautery with double-balloon endoscopy and diagnosed as a juvenile polyp pathologically. All clinical symptoms disappeared, and all laboratory data improved after treatment, without recurrence for more than one year after the procedure. Abdominal ultrasonographic screening and the fecal calprotectin value led to the diagnosis and non-surgical invasive treatment of an isolated small intestinal juvenile polyp

Ultrasonographic study of intestinal Doppler blood flow in infantile non-IgE-mediated gastrointestinal food allergy

Background: Although non-IgE-mediated gastrointestinal food allergy has increased rapidly in Japan, a small number of reports has evaluated B-mode and Doppler ultrasonographic findings in the acute phase of infantile gastrointestinal milk allergy. The aim of the present study was to compare the diagnostic utility of ultrasonographic findings and laboratory allergic data in non-IgE-mediated infantile gastrointestinal milk allergy. Methods: Sixteen cases of active non-IgE-mediated infantile gastrointestinal milk allergy, diagnosed by food elimination tests and oral food challenge tests (OFCTs) (group A), 15 cases of acute viral gastroenteritis (AGE) (group B), and 15 controls (group C) were enrolled. 1) B-mode abdominal ultrasound findings, 2) laboratory allergic data including eosinophil counts (Eos), serum IgE, and the antigen-specific lymphocyte proliferation test (ALPT) against milk protein, and 3) vessel density (VD) indirectly quantified by gastrointestinal Doppler flow at jejunum, ileum, and sigmoid colonic mucosae were evaluated and compared among the groups. Results: In the small intestine, wall thickening, dilation, mesenteric thickening, and poor peristalsis were found in 100%, 62.5%, 93.7%, and 100%, respectively, in group A. Eos, IgE, ALPT, and VD were positive in 25.0%, 0%, 87.5%, and 100%, respectively, in group A. Small intestinal VD was significantly greater in group A than in groups B (jejunum p < .001; ileum p < .001) and C (jejunum p < .001; ileum p < .001), with no significant differences between groups B and C (jejunum: p = .74; ileum: p = .73). Conclusions: Abdominal Doppler ultrasonography and small intestinal VD at symptomatic state can support the diagnosis and evaluation of non-IgE-mediated infantile gastrointestinal milk allergy with symptoms of vomiting, diarrhea, and failure to thrive. Keywords: Doppler ultrasound imaging, Eosinophilia, Infant, Milk allergy, Serological tes