Refractory to treat Helicobacter cinaedi bacteremia with bilateral lower extremities cellulitis in an immunocompetent patient

AbstractHelicobacter cinaedi is known to cause bacteremia with multi-focal cellulitis, usually, among immunocompromised patients. We report here a 54-year-old Japanese man who was found to have bacteremia complicated with bilateral lower extremities cellulitis due to H. cinaedi. This patient did not have any immunocompromised conditions including Human Immunodeficiency Virus infection. In this patient, the cellulitis was multi-focal which is rare among immunocompetent patients. In addition, interestingly, the cellulitis was symmetrically on the both sides on the lower dorsal part of the extremities. The patient was treated with meropenem, which was considered as one of the best available agents, however, he required a prolonged antimicrobial treatment. During the admission, he underwent colonoscopy which was unremarkable, and his stool culture was also negative while on meropenem. Subsequently, he developed recurrent symptoms of the right lower extremity twice and each time he was treated with intravenous meropenem followed by oral minocycline. After the total of 12 weeks of antimicrobial treatment, his symptoms subsided. Clinicians should be aware of this organism when treating multi-focal, or symmetrical cellulitis even if the patients are immunocompetent

Campylobacter fetus meningitis associated with eating habits of raw meat and raw liver in a healthy patient: A case report and literature review

Meningitis caused by the zoonotic pathogen Campylobacter fetus in immunocompetent adults is rare. We report a 48-year-old Japanese woman with no underlying disease who was found to have meningitis caused by C. fetus. Both C. fetus subsp. fetus and C. fetus subsp. venerealis were isolated from the cerebrospinal fluid culture. The mode of infection in our patient was considered to be associated with the consumption of raw beef and raw cattle liver on a regular basis. Public awareness and education to avoid the consumption of raw or undercooked meat might help prevent C. fetus meningitis

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

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

Bacteremic renal stone-associated urinary tract infection caused by nontypable Haemophilus influenzae: A rare invasive disease in an immunocompetent patient

Haemophilus species are known to colonize the upper respiratory tract and can cause infections. However Haemophilus influenzae has been rarely described as a cause of genitourinary tract infection. We report a 44-year-old nonimmunocompromised Japanese man with bacteremic pyelonephritis caused by a nontypable H. influenzae associated with a left ureteral calculus. The organism was isolated from both blood and urine cultures. Treatment consisted of 14 days of intravenous ceftriaxone and oral amoxicillin one after than other and insertion of a left ureteral stent. After discharge, he underwent extracorporeal shock wave lithotrity for the left ureteral calculus. He had no recrudescence of the symptoms. H. influenzae should be considered as a genitourinary pathogen among patients with certain risk factors such as anatomical or functional abnormality of genitourinary tract. Collaboration between clinicians and microbiology laboratory personnel is essential for correct identification of the organism and appropriate therapy for genitourinary tract infections due to this organism

Campylobacter fetus meningitis associated with eating habits of raw meat and raw liver in a healthy patient: A case report and literature review

Meningitis caused by the zoonotic pathogen Campylobacter fetus in immunocompetent adults is rare. We report a 48-year-old Japanese woman with no underlying disease who was found to have meningitis caused by C. fetus. Both C. fetus subsp. fetus and C. fetus subsp. venerealis were isolated from the cerebrospinal fluid culture. The mode of infection in our patient was considered to be associated with the consumption of raw beef and raw cattle liver on a regular basis. Public awareness and education to avoid the consumption of raw or undercooked meat might help prevent C. fetus meningitis

Challenges in treatment of disseminated nocardiosis in an elderly patient with renal failure on corticosteroids: a case report

We report the case of a 71-year-old Japanese man with a history of chronic kidney disease and sarcoidosis receiving chronic corticosteroids who presented with disseminated Nocardia brasiliensis infection. He initially showed improvement with empiric antimicrobial therapy including trimethoprim-sulfamethoxazole. However, he deteriorated after modifying the empiric regimen due to complicated hyperkalemia and ultimately died. In general, elderly patients have decreased renal function. Standard therapy for nocardiosis with trimethoprim-sulfamethoxazole may not be used for a prolonged period of time. This case emphasizes the challenges and importance of prudent selection of empiric antimicrobial therapy for disseminated nocardiosis in elderly patients with underlying kidney disease

Impact of regional heterogeneity on the severity of COVID-19

The main objective of the study is to assess the impact of regional heterogeneity on the severity of COVID-19 in Japan. We included 27,865 cases registered between January 2020 and February 2021 in the COVID-19 Registry of Japan, to examine the relationship between the National Early Warning Score (NEWS) of COVID-19 patients on the day of admission and the prefecture where the patients live. A hierarchical Bayesian model was used to examine the random effect of each prefecture in addition to the patients’ backgrounds. Additionally, we compared the results of two models; one model included the number of beds secured for COVID-19 patients in each prefecture as one of the fixed effects, and the other model did not. The results indicated that the prefecture had a substantial impact on the severity of COVID-19 on admission, even when considering the effect of the number of beds separately. Our analysis revealed a possible association between regional heterogeneity and increased/decreased risk of severe COVID-19 infection on admission. This heterogeneity was derived not only from the number of beds secured in each prefecture but also from other factors

Outbreak of Trichinella T9 Infections Associated with Consumption of Bear Meat, Japan

An outbreak of trichinellosis occurred in Japan in December 2016. All case-patients had eaten undercooked bear meat, from which Trichinella larvae were subsequently isolated. DNA sequencing analysis of the mitochondrial genes cytochrome c-oxidase subunit 1 and internal transcribed spacer 2 confirmed that Trichinella T9 had caused the outbreak