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Tsuyoshi Sekizuka, Kentaro Itokawa, Rina Tanaka, Masanori Hashino, Koji Yatsu, Makoto Kuroda Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, 162-8640, JapanCorrespondence: Makoto Kuroda, Pathogen Genomics Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjyuku, Tokyo, 162-8640, Japan, Tel +81-3-5285-1111, Fax +81-3-5285-1166, Email makokuro@niid.go.jpPurpose: Urban wastewater treatment plant (WWTP) effluents, even with proper treatment, may cause antimicrobial resistance (AMR) burden, with a high frequency of acquired antimicrobial resistance genes (ARGs). The dissemination of ARGs into the environment increases the risk of infectious diseases; however, there is little direct evidence regarding their epidemiological effects. This study aimed to assess effluents from urban WWTPs around the Tama River and Tokyo Bay using metagenomic analysis of (AMR) genes (ARGs) and heavy-metal resistance genes.Methods: Metagenomic DNA-seq analysis of water samples and resistome analysis were performed.Results: The most prevalent ARG was the sulfonamide resistance gene, sul1, followed by the quaternary ammonium compound resistance gene, qacE, suggesting that basic gene sets (sul1 and ∆qacE) in the class 1 integrons are the predominant ARGs. The aminoglycoside resistance genes, aadA and aph, and macrolide resistance genes, msr(E) and mph(E), were the predominant ARGs against each antimicrobial. blaOXA and blaGES were frequently detected, whereas the blaCTX-M cluster was faintly detected. Non-metric multidimensional scaling plot analysis and canonical correspondence analysis results suggested that marked differences in ARGs could be involved in the seasonal differences; qnrS2, aac(6’)-Ib, and mef(C) increased markedly in summer, whereas msr(E) was more frequently detected in winter. Heavy-metal (Hg and Cu) resistance genes (HMRGs) were significantly detected in effluents from all WWTPs.Conclusion: We characterized a baseline level of the environmental ARG/HMRG profile in the overall community, suggesting that environmental AMR surveillance, particularly in urban WWTPs, is a valuable first step in monitoring the AMR dissemination of bacteria from predominantly healthy individuals carrying notable ARG/Bs.Keywords: urban sewage, effluent, metagenomics, Enterobacteriaceae, ESBL, carbapenemase, heavy-metal resistance

Miwa Katagiri,1,2 Makoto Kuroda,2 Tsuyoshi Sekizuka,2 Norihide Nakada,3 Yukitaka Ito,4 Masanobu Otsuka,4 Manabu Watanabe,1 Shinya Kusachi1 1Department of Surgery, Toho University Ohashi Medical Center, Meguro-ku, Tokyo, Japan; 2Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan; 3Research Center for Environmental Quality Management, Graduate School of Engineering, Kyoto University, Otsu-shi, Shiga, Japan; 4Division of Clinical Microbiology Laboratory, Toho University Ohashi Medical Center, Meguro-ku, Tokyo, JapanCorrespondence: Miwa KatagiriDepartment of Surgery, Toho University Ohashi Medical Center, 2-22-36 Ohashi, Meguro-ku, Tokyo, 153-8515, JapanTel +81354333086Fax +81354333091Email girioyoshikazu0513@gmail.comMakoto KurodaLaboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, JapanTel +81352851111Fax +81352851150Email makokuro@niid.go.jpBackground: Excrement containing antimicrobial-resistant bacteria (ARB) is discharged from the hospital sewage through wastewater treatment plants (WWTP) into rivers, increasing the antimicrobial resistance (AMR) burden on the environment.Purpose: We illustrate the contamination of hospital sewage tanks with ARB harboring antimicrobial resistance genes (ARGs) using comprehensive metagenomic sequencing. During the study period, we moved to a new hospital building constructed for renovation. Therefore, we investigated the difference in bacterial flora in the sewage tanks for each building with different departments, and the change in bacterial flora over time in new sewage tanks. Furthermore, we performed a comparative genome analysis of extended spectrum β-lactamase (ESBL)-producing organisms (EPOs) from hospital sewage and clinical samples. Residual antibiotics in the sewage tank were also measured.Methods: Metagenomic analysis was performed on the hospital sewage samples, followed by whole genome sequencing of EPOs.Results: The bacterial composition of new sewage tanks was comparable with that of old tanks within 1 month after relocation and was instantly affected by excrement. The bacterial composition of sewage tanks in the old and new buildings, containing rooms where seriously ill patients were treated, was similar. Selection on CHROMagar ESBL allowed detection of EPOs harboring blaCTX-M and carbapenemase genes in all sewage tanks. One of the sewage Escherichia coli strain comprising ST393 harboring blaCTX-M-27 corresponded to the clinical isolates based on core genome analysis. Moreover, the levels of levofloxacin and clarithromycin in the hospital sewage were 0.0325 and 0.0135 μg/mL, respectively.Conclusion: Hospital sewage was contaminated with many ARB species, ARGs and residual antibiotics, which can cause a burden on WWTP sewage treatment. The bacterial flora in the sewage tank was rapidly affected, especially by the ward with seriously ill patients. AMR monitoring of hospital sewage may help detect carriers prior to nosocomial ARB-associated outbreaks and control the outbreaks.Keywords: hospital sewage, antimicrobial resistance, antimicrobial resistance gene, metagenome analysis, whole genome sequencing, residual antimicrobial reagents

Yoko Takayama, 1, 2 Tsuyoshi Sekizuka, 3 Hidehito Matsui, 4 Yuzuru Adachi, 4 Ryotaro Eda, 5 Shin Nihonyanagi, 2 Tatsuhiko Wada, 2 Mari Matsui, 6 Satowa Suzuki, 6 Masashi Takaso, 7 Hidero Kitasato, 5 Makoto Kuroda, 3 Hideaki Hanaki 4 1Department of Infection Control and Infectious Diseases, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Kanagawa, Japan; 2Department of Infection Control and Prevention, Kitasato University Hospital, Kanagawa, Japan; 3Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan; 4Infection Control Research Center, Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan; 5Department of Microbiology, School of Allied Health Sciences, Kitasato University, Kanagawa, Japan; 6Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan; 7Department of Orthopaedic Surgery, Kitasato University School of Medicine, Kanagawa, JapanCorrespondence: Yoko Takayama 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0374, JapanTel/Fax +81-42-778-9119Email yoko@med.kitasato-u.ac.jpPurpose: New Delhi metallo-β-lactamase 5 (NDM-5) shows stronger resistance to carbapenems and broad-spectrum cephalosporins than NDM-1 because NDM-5 differs from NDM-1 by two amino acid substitutions. In this study, our aim was to characterize a NDM-5-producing Escherichia coli isolate KY1497 from a patient with urinary tract infection in Japan, who had no recent history of overseas travel.Patients and Methods: NDM-5-producing E. coli isolate KY1497 was detected in the urine sample of a patient hospitalized in a tertiary hospital in Japan. The complete genome sequence of isolate KY1497 was determined by short- and long-read sequencing with hybrid assembly, followed by multilocus sequence typing (MLST), core-genome phylogeny analysis, plasmid analysis, and transconjugation experiments.Results: KY1497 was classified as ST405 by MLST, and core-genome phylogeny exhibited the closest lineage to the clinical isolates in Nepal (IOMTU605) and Canada (FDAARGOS_448). KY1497 harbors blaNDM-5 in the IncFII-IncFIB(pB171) replicon plasmid (pKY1497_1, 123,767 base pairs). Plasmid analysis suggested that the cognate plasmids of pKY1497_1 have a minor plasmid background, rather than the globally disseminated IncX3 plasmid carrying blaNDM-5. Transconjugation analysis revealed that pKY1497_1 is transmissible to the recipient E. coli J53 strain.Conclusion: We characterized a novel Inc replicon plasmid (IncFII-IncFIB[pB171]) carrying blaNDM-5 and its host E. coli strain. NDMs are associated with a high risk of infection worldwide because of their antibiotic resistance and untreatable and hard-to-treat infections. Other patients in the hospital showed negative results for carbapenem-resistant Enterobacteriaceae. As NDM-producing strains are only sporadically detected in Japan, attention should be provided to the community prevalence of NDM-producing E. coli strains to prevent nosocomial infections.Keywords: blaNDM-5, Escherichia coli, sequence type 405, IncFII, IncFIB

Tsuyoshi Sekizuka, Yuba Inamine, Takaya Segawa, Makoto KurodaLaboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Shinjuku, Tokyo, JapanPurpose: New Delhi metallo-β-lactamase (NDM)-5-producing Enterobacteriaceae have been detected in rivers, sewage, and effluents from wastewater treatment plants (WWTPs). Environmental contamination due to discharged effluents is of particular concern as NDM variants may be released into waterways, thereby posing a risk to humans. In this study, we collected effluent samples from a WWTP discharged into a canal in Tokyo Bay, Japan.Methods: Testing included the complete genome sequencing of Escherichia coli GSH8M-2 isolated from the effluent as well as a gene network analysis.Results: The complete genome sequencing of GSH8M-2 revealed that it was an NDM-5-producing E. coli strain sequence type ST542, which carries multiple antimicrobial resistance genes for β-lactams, quinolone, tetracycline, trimethoprim-sulfamethoxazole, florfenicol/chloramphenicol, kanamycin, and fosfomycin. The blaNDM-5 gene was found in the IncX3 replicon plasmid pGSH8M-2-4. Gene network analysis using 142 IncX3 plasmid sequences suggested that pGSH8M-2-4 is related to both clinical isolates of E. coli and Klebsiella species in Eastern Asia. GSH8M-2 also carries the blaCTX-M-55 gene in IncX1 plasmid pGSH8M-2-3.Conclusion: This is the first report of environmental NDM-5-producing E. coli isolated from a WWTP in Japan. NDM-5 detection is markedly increasing in veterinary and clinical settings, suggesting that dual β-lactamases, such as NDM-5 and CTX-M-55, might be acquired through multiple steps in environment settings. Environmental contamination through WWTP effluents that contain producers of NDM variants could be an emerging potential health hazard. Thus, regular monitoring of WWTP effluents is important for the detection of antimicrobial-resistant bacteria that may be released into the waterways and nearby communities.Keywords: sewage, carbapenemase, NDM-5, IncX3, CTX-M-55, IncX1

Abstract Background At present, six accessible sequences of 16S rDNA from Taylorella equigenitalis (T. equigenitalis) are available, whose sequence differences occur at a few nucleotide positions. Thus it is important to determine these sequences from additional strains in other countries, if possible, in order to clarify any anomalies regarding 16S rDNA sequence heterogeneity. Here, we clone and sequence the approximate full-length 16S rDNA from additional strains of T. equigenitalis isolated in Japan, Australia and France and compare these sequences to the existing published sequences. Results Clarification of any anomalies regarding 16S rDNA sequence heterogeneity of T. equigenitalis was carried out. When cloning, sequencing and comparison of the approximate full-length 16S rDNA from 17 strains of T. equigenitalis isolated in Japan, Australia and France, nucleotide sequence differences were demonstrated at the six loci in the 1,469 nucleotide sequence. Moreover, 12 polymorphic sites occurred among 23 sequences of the 16S rDNA, including the six reference sequences. Conclusion High sequence similarity (99.5% or more) was observed throughout, except from nucleotide positions 138 to 501 where substitutions and deletions were noted.

Foodborne disease outbreaks caused by raw olive flounders ( Paralichthys olivaceus) parasitized with Kudoa septempunctata have been reported in Japan. Origins of olive flounders consumed in Japan vary, being either domestic or imported, and aquaculture-raised or natural. Although it is unknown whether different sources are associated with different outcomes, it is desirable to identify whether this is the case by determining whether unique K. septempunctata strains occur and if so, whether some are associated with foodborne illness. We here developed an intraspecific genotyping method, using the sequence variation of mitochondrial genes. We collected olive flounder samples from foodborne disease outbreaks, domestic fish farms or quarantine offices and investigated whether K. septempunctata genotype is associated with pathogenicity or geographic origin. The 104 samples were classified into three genotypes, ST1, ST2 and ST3. Frequency of symptomatic cases differed by genotypes, but the association was not statistically significant. Whereas K. septempunctata detected from aquaculture-raised and natural fish from Japan were either ST1 or ST2, those from fish inspected at quarantine from Korea to Japan were ST3. Our method can be applied to phylogeographic analysis of K. septempunctata and contribute to containing the foodborne disease. The genotype database is hosted in the Pub MLST website (). [ABSTRACT FROM AUTHOR]

We aimed to analyze the situation of the first two epidemic waves in Myanmar using the publicly available daily situation of COVID-19 and whole-genome sequencing data of SARS-CoV-2. From March 23 to December 31, 2020, there were 33,917 confirmed cases and 741 deaths in Myanmar (case fatality rate of 2.18%). The first wave in Myanmar from March to July was linked to overseas travel, and then a second wave started from Rakhine State, a western border state, leading to the second wave spreading countrywide in Myanmar from August to December 2020. The estimated effective reproductive number (Rt) nationwide reached 6–8 at the beginning of each wave and gradually decreased as the epidemic spread to the community. The whole-genome analysis of 10 Myanmar SARS-CoV-2 strains together with 31 previously registered strains showed that the first wave was caused by GISAID clade O or PANGOLIN lineage B.6 and the second wave was changed to clade GH or lineage B.1.36.16 with a close genetic relationship with other South Asian strains. Constant monitoring of epidemiological situations combined with SARS-CoV-2 genome analysis is important for adjusting public health measures to mitigate the community transmissions of COVID-19.

Human parechovirus has rarely been shown to cause clinical disease in adults. During June-August 2008, a total of 22 adults sought treatment at Yonezawa City Hospital in Yamagata, Japan, for muscle pain and weakness of all limbs; most also had fever and sore throat. All patients received a clinical diagnosis of epidemic myalgia; clinical laboratory findings suggested an acute inflammatory process. Laboratory confirmation of infection with human parechovirus type 3 (HPeV3) was made for 14 patients; we isolated HPeV3 from 7 patients, detected HPeV3 genome in 11, and observed serologic confirmation of infection in 11. Although HPeV3 is typically associated with disease in young children, our results suggest that this outbreak of myalgia among adults was associated with HPeV3 infection. Clinical consideration should be given to HPeV3 not only in young children but also in adults when an outbreak occurs in the community. [ABSTRACT FROM AUTHOR]

The PCR amplicons (about 1450 bp in length) of flaA gene fragments of 11 isolates of urease-positive thermophilic Campylobacter (UPTC) isolated from the natural environment not including wild birds in Northern Ireland were demonstrated to be shorter than those of C. jejuni 81116 and six isolates of C. jejuni and C. coli (about 1700 bp) isolated in Northern Ireland and Japan. When the nucleotide lengths of the possible open reading frame (ORF) of the flaA genes were determined, those from the 11 UPTC isolates were estimated to be 1464–1503 bp, and those from the six C. jejuni and C. coli isolates and C. jejuni 81116 strain to be 1716–1728 bp. Nucleotide sequence and deduced amino acid sequence alignments of the possible ORFs demonstrated that the ORFs from the 11 UPTC isolates lack about 80 amino acid residues, mainly from the approximate residue numbers 390–470 of the large variable region in the flaA protein of the seven isolates of C. jejuni and C. coli, and do not have any internal termination codons. High amino acid sequence similarity of both amino- and carboxy-termini of the ORFs of the flaA gene was demonstrated between the 11 isolates of UPTC and the 7 isolates of C. jejuni and C. coli. The 11 UPTC isolates examined were strongly suggested to possess a shorter flaA gene without any internal termination codons. [ABSTRACT FROM AUTHOR]

Abstract Background Corynebacterium ulcerans can cause a diphtheria-like illness, especially when the bacterium is lysogenized with a tox gene-carrying bacteriophage that produces diphtheria toxin. Acquisition of toxigenicity upon phage lysogenization is a common feature of C. ulcerans and C. diphtheriae. However, because of a lack of C. ulcerans genome information, a detailed comparison of prophages has not been possible between these two clinically important and closely related bacterial species. Results We determined the whole genome sequence of the toxigenic C. ulcerans 0102 isolated in Japan. The genomic sequence showed a striking similarity with that of Corynebacterium pseudotuberculosis and, to a lesser extent, with that of C. diphtheriae. The 0102 genome contained three distinct prophages. One of these, ΦCULC0102-I, was a tox-positive prophage containing genes in the same structural order as for tox-positive C. diphtheriae prophages. However, the primary structures of the individual genes involved in the phage machinery showed little homology between the two counterparts. Conclusion Taken together, these results suggest that the tox-positive prophage in this strain of C. ulcerans has a distinct origin from that of C. diphtheriae NCTC 13129.

Abstract Background The combined sequences encoding a partial and putative rpsI open reading frame (ORF), non-coding (NC) region, a putative ORF for the Campylobacter adhesin to fibronectin-like protein (cadF), a putative Cla_0387 ORF, NC region and a partial and putative Cla_0388 ORF, were identified in 16 Campylobacter lari isolates, using two novel degenerate primer pairs. Probable consensus sequence at the -35 and -10 regions were identified in all C. lari isolates, as a promoter. Results Thus, cadF (-like) gene is highly conserved among C. lari organisms. Transcription of the cadF (-like) gene in C. lari cells in vivo was also confirmed and the transcription initiation site was determined. A peptidoglycan-associating alpha-helical motif in the C-terminal regions of some bacterial cell-surface proteins was completely conserved amongst the putative cadF (-like) ORFs from the C. lari isolates. Conclusion The putative cadF (-like) ORFs from all C. lari isolates were nine amino acid larger than those from C. jejuni, and showed amino acid residues 137 -140 of FALG (50% identity), instead of the FRLS residues of the maximal fibronectin-binding activity site demonstrated within C. jejuni CadF. A neighbor joining tree constructed based on cadF (-like) gene sequence information formed a major cluster consisting of C. lari isolates, separating from the other three thermophilic campylobacters.

Abstract Background Sequence information on the 16S-23S rDNA internal spacer region (ISR) exhibits a large degree of sequence and length variation at both the genus and species levels. A primer pair for the amplification of 16S-23S rDNA ISR generated three amplicons for each of isolates of Taylorella asinigenitalis (UCD-1T, UK-1 and UK-2). Findings Following TA cloning and sequencing, the three isolates of T. asinigenitalis were demonstrated to possess three ISR units of different lengths. Although the three corresponding ISRs (A, B and C) were identified to be identical to each other (UK-1 and UK-2 isolates), the ISRs shared approximately 95.3–98.9% nucleotide sequence similarities between the UCD-1T and UK-1/-2 isolates. A typical order of two intercistronic tRNA genes (5'-tRNAIle-tRNAAla-3') with the different nucleotide spacers [44 through 51 base pairs (bp)] in length was identified among the isolates. The consensus sequences of the antiterminators of boxB and boxA were also identified in all ISRs. Thus, three ISRs were identified for each isolate, and therefore, at least three distinctly different ribosomal RNA operons were suggested to occur in the genome of T. asinigenitalis. This was also confirmed by Southern hybridization procedure. Conclusion The present study represents a dendrogram constructed based on the nucleotide sequence data of 16S-23S rDNA ISR for T. asinigenitalis, which may aid in the phylogenetic positioning of T. asinigenitalis within the genus Taylorella, and in the molecular discrimination of T. asinigenitalis.

Background/Objectives : The cause of ulcerative colitis (UC) may be related to commensal bacteria in genetically susceptible patients. We previously demonstrated that triple antibiotic combination therapy induces remission in patients with active UC in randomized controlled trials (RCTs). Now, we investigate changes in the gut microbiota of patients who responded to the antibiotic combination therapy. Methods : Thirty-one patients with UC given ATM/AFM (amoxicillin, metronidazole, and tetracycline or fosfomycin) therapy for two weeks were enrolled in this study. The clinical conditions of these UC patients were evaluated by the partial Mayo score. The gut microbiota was compared via the metagenomic shot gun analysis of fecal samples. Results : Of the 31 patients, 16 and 8 experienced complete and partial remission, respectively, over three months in response to ATM/AFM therapy, whereas ATM/AFM showed no efficacy in 7 patients. The dysbiosis before treatment in the active stage could be associated with increased populations of Bacteroides , Parabacteroides , Rickenella , Clostridium , Flavonifractor , Pelagibacter , Bordetella , Massilia , and Piscrickettsia species. Metagenomic analysis revealed dramatic changes in the gut microbiota at an early stage, that is, just two weeks after starting ATM/AFM therapy. After treatment in the responder group, the populations of bifidobacterium and lactobacilli species were significantly increased, while the population of bacteroides decreased. Conclusions : These results suggest that metagenomic analysis demonstrated a marked change in the gut microbiota after antibiotic combination treatment. In the triple antibiotic combination therapy, remission was associated with an increase in bifidobacterium and lactobacilli species.

Ovarian clear cell carcinoma (OCCC) is a gynecological cancer with a dismal prognosis; however, the mechanism underlying OCCC chemoresistance is not well understood. To explore the intracellular networks associated with the chemoresistance, we analyze surgical specimens by performing integrative analyses that combine single-cell analyses and spatial transcriptomics. We find that a chemoresistant OCCC subpopulation with elevated HIF activity localizes mainly in areas populated by cancer-associated fibroblasts (CAFs) with a myofibroblastic phenotype, which is corroborated by quantitative immunostaining. CAF-enhanced chemoresistance and HIF-1α induction are recapitulated in co-culture assays, which show that cancer-derived platelet-derived growth factor (PDGF) contributes to the chemoresistance and HIF-1α induction via PDGF receptor signaling in CAFs. Ripretinib is identified as an effective receptor tyrosine kinase inhibitor against CAF survival. In the co-culture system and xenograft tumors, ripretinib prevents CAF survival and suppresses OCCC proliferation in the presence of carboplatin, indicating that combination of conventional chemotherapy and CAF-targeted agents is effective against OCCC., Competing Interests: Declaration of interests Teikyo University has filed for a patent application on CAF inhibition by tyrosine kinase inhibitors, and K.O. and Y.M. are named as inventors on this patent., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

We studied 226 patients in Toyama Prefecture who were notified of COVID-19 during the first wave between March 30 and May 18, 2020. Of the 226 patients, 22 (9.7%) died, most (95%) of whom were aged ≥65 years. A large cluster comprising 59 patients (41 residents and 18 staff members) was identified in a nursing home on April 17. No deaths occurred among staff members; however, 12 of the 41 residents (29%) died. Although the threshold cycle (Ct) values were significantly lower in the 20-64 and ≥65 years age groups than in the <20 years age group, no correlation was found between the Ct values and severity, fatal outcome, or secondary infection. The haplotype network of 145 SARS-CoV-2 isolates (64%) from 226 patients was analyzed. The viral genomes of the case groups differed by less than five nucleotide bases. These data suggest that the SARS-CoV-2 strains, which were initially introduced into Toyama Prefecture in late March and early April 2020, and their closely related strains, identified as lineage B.1.1, circulated during the first wave. The reduced inter-prefectural mobility of local residents may support the lack of strain diversity in SARS-CoV-2 during the first wave of the state of emergency.

Importance: C. tetani is a spore-forming, anaerobic bacterium that produces a toxin causing muscle stiffness and paralysis. Tetanus is preventable with the toxoid vaccine, but it remains a significant public health threat in regions with low vaccine coverage. However, there are relatively few isolates and limited genomic information available worldwide. In Japan, about 100 cases are reported each year, but there have been no nationwide surveys of isolates, and no genomic information from Japanese isolates has been published. In our study, we analyzed the genomes of 151 strains from a limited survey of soil in Kumamoto, Japan. Our findings revealed a high degree of genetic diversity, and we also identified a subset of strains that produced significantly more toxin, which provides new insights into the pathogenesis of tetanus. Our findings lay the foundation for future studies to investigate the distribution and evolution of C. tetani in Japan and neighboring countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Motohide Takahashi has received an advisory contract from The Chemo-Sero-Therapeutic Research Institute.

Objective: This study aimed to compare maternal outcomes of prenatally and nonprenatally diagnosed placenta accreta spectrum., Data Sources: A systematic literature search was performed in PubMed, the Cochrane database, and Web of Science until November 28, 2022., Study Eligibility Criteria: Studies comparing the clinical presentation of prenatally and nonprenatally diagnosed placenta accreta spectrum were included. The primary outcomes were emergent cesarean delivery, hysterectomy, blood loss volume, number of transfused blood product units, urological injury, coagulopathy, reoperation, intensive care unit admission, and maternal death. In addition, the pooled mean values for blood loss volume and the number of transfused blood product units were calculated. The secondary outcomes included maternal age, gestational age at birth, nulliparity, previous cesarean delivery, previous uterine procedure, assisted reproductive technology, placenta increta and percreta, and placenta previa., Methods: Study screening was performed after duplicates were identified and removed. The quality of each study and the publication bias were assessed. Forest plots and I 2 statistics were calculated for each study outcome for each group. The main analysis was a random-effects analysis., Results: Overall, 415 abstracts and 157 full-text studies were evaluated. Moreover, 31 studies were analyzed. Prenatally diagnosed placenta accreta spectrum was associated with a significantly lower rate of emergency cesarean delivery (odds ratio, 0.37; 95% confidence interval, 0.21-0.67), higher hysterectomy rate (odds ratio, 1.98; 95% confidence interval, 1.02-3.83), lower blood loss volume (mean difference, -0.65; 95% confidence interval, -1.17 to -0.13), and lower number of transfused red blood cell units (mean difference, -1.96; 95% confidence interval, -3.25 to -0.68) compared with nonprenatally diagnosed placenta accreta spectrum. The pooled mean values for blood loss volume and the number of transfused blood product units tended to be lower in the prenatally diagnosed placenta accreta spectrum groups than in the nonprenatally diagnosed placenta accreta spectrum groups. Nulliparity (odds ratio, 0.14; 95% confidence interval, 0.10-0.20), previous cesarean delivery (odds ratio, 6.81; 95% confidence interval, 4.12-11.25), assisted reproductive technology (odds ratio, 0.19; 95% confidence interval, 0.06-0.61), placenta increta and percreta (odds ratio, 3.97; 95% confidence interval, 2.24-7.03), and placenta previa (odds ratio, 6.81; 95% confidence interval, 4.12-11.25) showed statistical significance. No significant difference was found for the other outcomes., Conclusion: Despite its severity, the positive effect of prenatally diagnosed placenta accreta spectrum on outcomes underscores the necessity of a prenatal diagnosis. In addition, the pooled mean values provide a preoperative preparation guideline., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endometriosis is known to be associated with an increased risk of endometrioid and clear cell ovarian cancer. However, the association between endometriosis and endometrial cancer is controversial. Therefore, we retrospectively analyzed the medical records of women with endometrial cancer who had undergone surgery at our institution to evaluate the clinicopathological relationship between endometrial cancer and endometriosis. The study included 720 women pathologically diagnosed with endometrial cancer at our hospital between 2000 and 2020. The participants were allocated to two groups of patients with endometrial cancer: patients with endometriosis ( n = 101) and patients without endometriosis ( n = 619). Endometrial cancer patients with endometriosis were significantly younger (median age 54.0 vs. 58.0; p = 0.002). In addition, endometrial cancer patients with endometriosis had fewer pregnancies and deliveries (median pregnancy 1.58 vs. 1.99; p = 0.019, median delivery 1.25 vs. 1.56; p = 0.012). The percentage of patients classified as stage IA was significantly higher in those with endometrial cancer with endometriosis (68.3% vs. 56.4%; p = 0.029). In the analysis of synchronous ovarian cancer, the percentage of dual primary cancer was higher in patients with endometriosis (14.9% vs. 1.6%; p < 0.001). The association of young-onset early-stage endometrial cancer with endometriosis is an important finding that cannot be ignored clinically.

Background: Diabetic foot infections (DFIs) are the most common complications of diabetic foot ulcers (DFUs), and a significant cause of lower extremity amputation. In this study we used whole genome sequencing to characterize the clonal composition, virulence and resistance genetic determinants of 58 Staphylococcus/Mammaliicoccus spp. isolates from contralateral healthy skin and DFU from 44 hospitalized patients., Results: S. aureus (n = 32) and S. epidermidis (n = 10) isolates were recovered from both DFUs and healthy skin, whereas, S. haemolyticus (n = 8), M. sciuri (n = 1), S. hominis (n = 1) and S. simulans (n = 3) were recovered exclusively from healthy skin. In contrast, S. caprae (n = 2) and S. saprophyticus (n = 1) were recovered only from DFUs. Among S. aureus isolates, MRSA were present with high prevalence (27/32, 84.4%), 18 of which (66.7%) were from DFUs and 9 (33.3%) from healthy skin. In contrast, the coagulase-negative Staphylococcus (CoNS)/Mammaliicoccus isolates (n = 26), in particular S. epidermidis and S. haemolyticus were more prevalent in healthy skin, (10/26, 38.5%) and (8/26, 30.8%), respectively. MLST, spa and SCCmec typing classified the 32 S. aureus isolates into 6 STs, ST672, ST80, ST241, ST1, ST97, ST291 and 4 unknown STs (STNF); 8 spa types, t044, t037, t3841, t1247, t127, t639, t937 and t9432 and 2 SCCmec types, type IV and type III(A). Among CoNS, the S. epidermidis isolates belonged to ST54, ST35 and ST640. S. haemolyticus belonged to ST3, ST25, ST29, ST1 and ST56. The sole M. sciuri isolate was found to carry an SCCmec type III(A). A wide range of virulence genes and antimicrobial resistance genes were found among our isolates, with varying distribution between species or STs. The pan-genome analysis revealed a highly clonal population of Staphylococcus isolates, particularly among S. aureus isolates. Interestingly, the majority of S. aureus isolates including MRSA, recovered from the healthy skin and DFUs of the same patient belonged to the same clone and exhibited similar virulence/resistance genotype., Conclusions: Our study provides clinically relevant information on the population profile, virulence and antibiotic resistance of Staphylococcus/Mammaliicoccus spp. in DFIs, which could serve as a basis for further studies on these as well as other groups of pathogens associated with DFIs., (© 2023. The Author(s).)

Metagenomic sequencing (mDNA-seq) is one of the best approaches to address antimicrobial resistance (AMR) issues and characterize AMR genes (ARGs) and their host bacteria (ARB); however, the sensitivity provided is insufficient for the overall detection in wastewater treatment plant (WWTP) effluents because the effluent is well treated. This study investigated the multiplex hybrid capture (xHYB) method (QIAseq × HYB AMR Panel) and its potential to increase AMR assessment sensitivity. The mDNA-Seq analysis suggested that the WWTP effluents had an average of 104 reads per kilobase of gene per million (RPKM) for the detection of all targeted ARGs, whereas xHYB significantly improved detection at 601,576 RPKM, indicating an average 5,805-fold increase in sensitivity. For instance, sul1 was detected at 15 and 114,229 RPKM using mDNA-seq and xHYB, respectively. The bla CTX-M , bla KPC , and mcr gene variants were not detected by mDNA-Seq but were detected by xHYB at 67, 20, and 1,010 RPKM, respectively. This study demonstrates that the multiplex xHYB method could be a suitable evaluation standard with high sensitivity and specificity for deep-dive detection, highlighting a broader illustration of ongoing dissemination in the entire community.