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Microbiology Spectrum Dec 2023Understanding the role of the endoribonuclease non-structural protein 15 (nsp15) (EndoU) in coronavirus (CoV) infection and pathogenesis is essential for vaccine target...
Understanding the role of the endoribonuclease non-structural protein 15 (nsp15) (EndoU) in coronavirus (CoV) infection and pathogenesis is essential for vaccine target discovery. Whether the EndoU activity of CoV nsp15, as a virulence-related protein, has a diverse effect on viral virulence needs to be further explored. Here, we found that the transmissible gastroenteritis virus (TGEV) and feline infectious peritonitis virus (FIPV) nsp15 proteins antagonize SeV-induced interferon-β (IFN-β) production in human embryonic kidney 293 cells. Interestingly, compared with wild-type infection, infection with EnUmt-TGEV or EnUmt-FIPV did not change the IFN-β response or reduce viral propagation in immunocompetent cells. The results of animal experiments showed that EnUmt viruses did not reduce the clinical presentation and mortality caused by TGEV and FIPV. Our findings enrich the understanding of nsp15-mediated regulation of alpha-CoV propagation and virulence and reveal that the conserved functions of nonstructural proteins have diverse effects on the pathogenicity of CoVs.
Topics: Animals; Humans; Coronavirus; Virulence; Endoribonucleases; Uridylate-Specific Endoribonucleases; Coronavirus Infections
PubMed: 37938022
DOI: 10.1128/spectrum.02209-23 -
BMC Nephrology Mar 2024To validate an association between new inflammation and frequent peritoneal dialysis-associated peritonitis (PDAP).
OBJECTIVE
To validate an association between new inflammation and frequent peritoneal dialysis-associated peritonitis (PDAP).
MATERIALS AND METHODS
In China, retrospective clinical data were collected on 208 patients who received continuous ambulatory peritoneal dialysis (CAPD) between 2010 and 2021. The patients were divided into two groups: non-frequent PDAP (the interval between two peritonitis episodes of more than one year) and frequent PDAP (the interval between two peritonitis episodes of less than one year). Patients with their first episode of peritonitis had their age, gender, history of hypertension, diabetic disease, underlying renal disease, bacterial infection, and laboratory data collected. The outcomes of bacterial dispersion, systemic immune-inflammation index (SII), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), and risk variables associated with frequent PDAP were analyzed.
RESULTS
There are differences between the two groups in dialysis time (p = 0.006), hypertensive nephropathy (p = 0.038), staphylococcus (p = 0.035), white blood cells (p = 0.001), neutrophil (p < 0.01), lymphocyte (p < 0.01), platelet(p = 0.01), SII(p < 0.01), CRP/HDL-C (p = 0.002), CRP (p < 0.001), serum creatinine (p = 0.007), blood urea nitrogen (p = 0.05), serum magnesium (0.03), serum potassium (p = 0.007), and dialysate polymorphonuclear cells (p = 0.004). Multifactorial logistic regression analysis found that SII (p < 0.001), CRP/HDL-C (p = 0.041), and Diabetes mellitus (p = 0.027) were independent risk factors for frequent PDAP. The ROC curve analysis revealed that combining SII with CRP/HDL-C resulted in the largest AUC area (AUC = 0.814).
CONCLUSIONS
Our findings offer clinical proof of the combination of SII and CRP/HDL-C in patients with frequent PDAP.
Topics: Humans; Retrospective Studies; Renal Dialysis; Inflammation; Peritonitis; Peritoneal Dialysis; Cholesterol, HDL
PubMed: 38443857
DOI: 10.1186/s12882-024-03496-z -
Journal of Nephrology Sep 2023This systematic review summarises the stability of less commonly prescribed antibiotics in different peritoneal dialysis solutions that could be used for... (Review)
Review
BACKGROUND
This systematic review summarises the stability of less commonly prescribed antibiotics in different peritoneal dialysis solutions that could be used for culture-directed therapy of peritonitis, which would be especially useful in regions with a high prevalence of multidrug antibiotic-resistant strains.
METHODS
A literature search of Medline, Scopus, Embase and Google Scholar for articles published from inception to 25 January, 2023 was conducted. Only antibiotic stability studies conducted in vitro and not recently reviewed by So et al. were included. The main outcomes were chemical, physical, antimicrobial and microbial stability. This protocol was registered in PROSPERO (registration number CRD42023393366).
RESULTS
We screened 1254 abstracts, and 28 articles were included in the study. In addition to those discussed in a recent systematic review (So et al., Clin Kidney J 15(6):1071-1078, 2022), we identified 18 antimicrobial agents. Of these, 9 have intraperitoneal dosing recommendations in the recent International Society for Peritoneal Dialysis (ISPD) peritonitis guidelines, and 7 of the 9 had stability data applicable to clinical practice. They were cefotaxime, ceftriaxone, daptomycin, ofloxacin, and teicoplanin in glucose-based solutions, tobramycin in Extraneal solution only and fosfomycin in Extraneal, Nutrineal, Physioneal 1.36% and 2.27% glucose solutions.
CONCLUSIONS
Physicochemical stability has not been demonstrated for all antibiotics with intraperitoneal dosing recommendations in the ISPD peritonitis guidelines. Further studies are required to determine the stability of antibiotics, especially in icodextrin-based and low-glucose degradation products, pH-neutral solutions.
Topics: Humans; Anti-Bacterial Agents; Dialysis Solutions; Glucose; Icodextrin; Peritoneal Dialysis; Peritonitis
PubMed: 37548827
DOI: 10.1007/s40620-023-01716-7 -
The Lancet. Healthy Longevity Sep 2023Infectious diseases are the leading cause of deaths in adults aged 65 years or older. Studies of adverse infection outcomes have been limited to specific infections and...
BACKGROUND
Infectious diseases are the leading cause of deaths in adults aged 65 years or older. Studies of adverse infection outcomes have been limited to specific infections and acute episodes and have not investigated longitudinal trends of cumulative infections. We aimed to identify distinct trajectories of longitudinal infection episodes in older adults and to assess their corresponding risk of all-cause mortality.
METHODS
In this retrospective cohort study, we included people aged 65 years or older who were admitted to hospital between Jan 1 and Dec 31, 2011, with one of the following infections: urinary tract, pneumonia, sepsis, cellulitis, cholecystitis, peritonitis, endocarditis, and meningitis. Participants were identified from Taiwan's National Health Insurance Research Database. We analysed infection episodes on a quarterly basis during a 5-year period (2011-15) and used group-based trajectory modelling to identify distinct trajectories. We examined the associations between infection trajectories and all-cause mortality using Kaplan-Meier curves and the Cox proportional hazard model.
FINDINGS
Among 79 666 eligible older adults, we identified four distinct infection trajectories over the 5-year follow-up: infrequent (58 619 [73·6%]), increasing (9746 [12·2%]), decreasing (9069 [11·4%]), and frequent (2232 [2·8%]). Compared with people with infrequent infections, the adjusted hazard ratios for all-cause mortality were 2·96 (95% CI 2·82-3·11) in participants with frequent infections, 2·15 (2·09-2·22) in those with increasing infections, and 1·85 (1·80-1·91) in those with decreasing infections.
INTERPRETATION
Older adults with multiple infection episodes, irrespective of type, pathogens, and distinct infection pattern, had greater risk of all-cause mortality compared with those with infrequent infections. Further research to define the overall infection burden in older adults is needed for risk stratification and to inform prevention strategies.
FUNDING
The Interdisciplinary Research Center for Healthy Longevity of National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education, the National Science and Technology Council, and the Ministry of Science and Technology in Taiwan.
Topics: Humans; Aged; Retrospective Studies; Taiwan; Research; Interdisciplinary Research; Aleurites
PubMed: 37659432
DOI: 10.1016/S2666-7568(23)00138-1 -
Science Signaling Jul 2023Uncontrolled inflammation is linked to poor outcomes in sepsis and wound healing, both of which proceed through distinct inflammatory and resolution phases. Eicosanoids...
Uncontrolled inflammation is linked to poor outcomes in sepsis and wound healing, both of which proceed through distinct inflammatory and resolution phases. Eicosanoids are a class of bioactive lipids that recruit neutrophils and other innate immune cells. The interaction of ceramide 1-phosphate (C1P) with the eicosanoid biosynthetic enzyme cytosolic phospholipase A (cPLA) reduces the production of a subtype of eicosanoids called oxoeicosanoids. We investigated the effect of shifting the balance in eicosanoid biosynthesis on neutrophil polarization and function. Knockin mice expressing a cPLA mutant lacking the C1P binding site (α mice) showed enhanced and sustained neutrophil infiltration into wounds and the peritoneum during the inflammatory phase of wound healing and sepsis, respectively. The mice exhibited improved wound healing and reduced susceptibility to sepsis, which was associated with an increase in anti-inflammatory N2-type neutrophils demonstrating proresolution behaviors and a decrease in proinflammatory N1-type neutrophils. The N2 polarization of α neutrophils resulted from increased oxoeicosanoid biosynthesis and autocrine signaling through the oxoeicosanoid receptor OXER1 and partially depended on OXER1-dependent inhibition of the pentose phosphate pathway (PPP). Thus, C1P binding to cPLAα suppresses neutrophil N2 polarization, thereby impairing wound healing and the response to sepsis.
Topics: Animals; Mice; Neutrophils; Sepsis; Autocrine Communication; Group IV Phospholipases A2; Inflammation
PubMed: 37433004
DOI: 10.1126/scisignal.add6527 -
Clinical Kidney Journal Dec 2023The aim of this study was to evaluate the impact of peritoneal dialysis (PD) strategy on technique and patient survival.
BACKGROUND
The aim of this study was to evaluate the impact of peritoneal dialysis (PD) strategy on technique and patient survival.
METHODS
This was a retrospective, single-center study conducted on consecutive patients with chronic kidney disease who underwent PD between January 2009 and December 2019. The study sample was stratified into four different groups according to PD technique [automated (APD) or manual (CAPD)] and icodextrin use (yes versus no). The primary endpoints were survival of both technique and patient.
RESULTS
A total of 531 patients were included in the analysis. Mean ± standard deviation age was 60.6 ± 14.6 years, 68.4% (363) were men and 34.8% (185) had diabetes. The median technique survival time was 19 (15) months. A total of 185 (34.8%), 96 (18.1%), 99 (18.7%) and 151 (28.4%) patients were included in the CAPD/No-Icodextrin, CAPD/Icodextrin, APD/No-Icodextrin and APD/Icodextrin study groups, respectively. Throughout the study, 180 (33.9%) patients underwent renal transplant, 71 (13.4%) were changed to hemodialysis and 151 (28.4%) died. Age [hazard ratio (HR) 0.975, 95% confidence interval (CI) 0.960-0.990, = .001] and incidence of early peritoneal infection (HR 2.440, 95% CI 1.453-4.098, = .001) were associated with technique survival, while age (HR 1.029, 95% CI 1.013-1.045, < .001), Charlson Index (HR 1.192, 95% CI 1.097-1.295, < 0.001), use of icodextrin (HR 0.421, 95% CI 0.247-0.710, < .001) and APD/Icodextrin (HR 0.499, 95% CI 0.322-0.803, = .005) were associated with patient survival.
CONCLUSIONS
Icodextrin use and APD/Icodextrin had a positive impact on patient survival, while older age and higher Charlson Index had a negative one. Age and incidence of early peritoneal infection significantly impacted on technique survival.
PubMed: 38046044
DOI: 10.1093/ckj/sfad155 -
PloS One 2023Edwardsiella ictaluri is a Gram-negative facultative intracellular fish pathogen causing enteric septicemia of catfish (ESC). While various secretion systems contribute...
Edwardsiella ictaluri is a Gram-negative facultative intracellular fish pathogen causing enteric septicemia of catfish (ESC). While various secretion systems contribute to E. ictaluri virulence, the Type VI secretion system (T6SS) remains poorly understood. In this study, we constructed 13 E. ictaluri T6SS mutants using splicing by overlap extension PCR and characterized them, assessing their uptake and survival in channel catfish (Ictalurus punctatus) peritoneal macrophages, attachment and invasion in channel catfish ovary (CCO) cells, in vitro stress resistance, and virulence and efficacy in channel catfish. Among the mutants, EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO exhibited reduced replication inside peritoneal macrophages. EiΔevpM, EiΔevpN, and EiΔevpO showed significantly decreased attachment to CCO cells, while EiΔevpN and EiΔevpO also displayed reduced invasion of CCO cells (p < 0.05). Overall, T6SS mutants demonstrated enhanced resistance to oxidative and nitrosative stress in the nutrient-rich medium compared to the minimal medium. However, EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO were susceptible to oxidative stress in both nutrient-rich and minimal medium. In fish challenges, EiΔevpD, EiΔevpE, EiΔevpG, EiΔevpJ, and EiΔevpK exhibited attenuation and provided effective protection against E. ictaluri wild-type (EiWT) infection in catfish fingerlings. However, their attenuation and protective efficacy were lower in catfish fry. These findings shed light on the role of the T6SS in E. ictaluri pathogenesis, highlighting its significance in intracellular survival, host cell attachment and invasion, stress resistance, and virulence. The attenuated T6SS mutants hold promise as potential candidates for protective immunization strategies in catfish fingerlings.
Topics: Animals; Edwardsiella ictaluri; Type VI Secretion Systems; Virulence; Ictaluridae; Catfishes; Enterobacteriaceae Infections; Fish Diseases
PubMed: 38153949
DOI: 10.1371/journal.pone.0296132 -
Renal Failure Dec 2023This study aimed to investigate the association between patient clinical characteristics and technique failure in peritoneal dialysis-related peritonitis (PDRP). The...
OBJECTIVE
This study aimed to investigate the association between patient clinical characteristics and technique failure in peritoneal dialysis-related peritonitis (PDRP). The effect of peritonitis-associated technique failure on patient survival was also assessed.
METHODS
Patients diagnosed with PDRP from January 1, 2010 to June 30, 2022 were retrospectively reviewed and analyzed. Relevant demographic, biochemical, and clinical data were collected. Univariate and multivariate logistic regression analyses were used to determine the predictors of peritonitis-associated technique failure in PD. Patients were divided into technique failure (F group) and nontechnique failure (NF group) groups. Patients were followed until death or until the date of Oct 1, 2022. Kaplan-Meier survival curves and landmark analysis were used to assess the survival of the PDRP cohort. Cox regression models were used to assess the association between potential risk factors and mortality.
RESULTS
A total of 376 patients with 648 cases of PDRP were included in this study. Multivariate logistic regression analysis demonstrated that peritoneal dialysis (PD) duration (OR = 1.12 [1.03, 1.21], = 0.005), dialysate WBC count on Day 3 after antibiotic therapy (OR = 1.41 [1.22, 1.64], 0.001), blood neutrophil-to-lymphocyte ratio (NLR) (OR = 1.83 [1.25, 2.70], = 0.002), and serum lactate dehydrogenase (LDH) (OR = 4.13 [1.69, 10.11], = 0.002) were independent predictors for technique failure in PDRP. Furthermore, serum high-density lipoprotein (HDL) (OR = 0.28 [0.13, 0.64], = 0.002) was a protective factor against technique failure. According to the Kaplan-Meier analysis, patients experiencing peritonitis-associated technique failure had lower postperitonitis survival (log-rank = 4.326, = 0.038). According to the landmark analysis, patients with a history of peritonitis-associated technical failures had a higher 8-year mortality after peritoneal dialysis. A Cox model adjusted for plausible predetermined confounders showed that technique failure was independently associated with all-cause mortality.
CONCLUSIONS
Dialysate WBC count on Day 3, PD duration, NLR, and LDH were independent risk factors for technique failure, whereas HDL was a protective factor. Peritonitis-associated technique failure had a higher risk of mortality and adverse effects on postperitonitis survival.
Topics: Humans; Retrospective Studies; Peritoneal Dialysis; Dialysis Solutions; Risk Factors; Peritonitis; Kidney Failure, Chronic
PubMed: 37125594
DOI: 10.1080/0886022X.2023.2205536 -
Genes Apr 2024Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained... (Review)
Review
INTRODUCTION
Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation.
CONCLUSIONS
This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.
Topics: Humans; Peritoneal Dialysis; Cell-Free Nucleic Acids; DNA, Mitochondrial; Biomarkers; MicroRNAs; DNA, Bacterial; Peritonitis; Peritoneum
PubMed: 38790182
DOI: 10.3390/genes15050553 -
Journal of Nephrology Sep 2023Peritonitis remains a significant complication of peritoneal dialysis. However, there is limited information on the clinical characteristics and outcomes of...
BACKGROUND
Peritonitis remains a significant complication of peritoneal dialysis. However, there is limited information on the clinical characteristics and outcomes of hospital-acquired peritonitis compared to community-acquired peritonitis in patients undergoing peritoneal dialysis. Furthermore, the microbiology and outcomes of community-acquired peritonitis may vary from hospital-acquired peritonitis. Therefore, the aim was to gather and analyse data to address this gap.
METHODS
Retrospective review of the medical records of all adult patients on peritoneal dialysis within the peritoneal dialysis units in four university teaching hospitals in Sydney, Australia, who developed peritonitis between January 2010 and November 2020. We compared the clinical characteristics, microbiology and outcomes of community-acquired peritonitis and hospital-acquired peritonitis. Community acquired peritonitis was defined as the development of peritonitis in the outpatient setting. Hospital-acquired peritonitis was defined as: (1) developed peritonitis anytime during hospitalisation for any medical condition other than peritonitis, (2) diagnosed with peritonitis within 7 days of hospital discharge and developed symptoms of peritonitis within 3 days of the hospital discharge.
RESULTS
Overall, 904 episodes of peritoneal dialysis-associated peritonitis were identified in 472 patients, of which 84 (9.3%) episodes were hospital-acquired. Patients with hospital-acquired peritonitis had lower mean serum albumin levels compared to those with community-acquired peritonitis(22.95 g/L vs. 25.76 g/L, p = 0.002). At the time of diagnosis, lower median peritoneal effluent leucocyte and polymorph counts were observed with hospital-acquired peritonitis compared to community-acquired peritonitis (1236.00/mm vs. 3183.50/mm, p < 0.01 and 1037.00/mm vs. 2800.00/mm, p < 0.01, respectively). Higher proportions of peritonitis due to Pseudomonas spp. (9.5% vs. 3.7%, p = 0.020) and vancomycin-resistant Enterococcus (2.4% vs. 0.0%, p = 0.009), lower rates of complete cure (39.3% vs. 61.7%, p < 0.001), higher rates of refractory peritonitis (39.3% vs. 16.4%, p < 0.001) and higher all-cause mortality within 30 days of peritonitis diagnosis (28.6% vs. 3.3%, p < 0.001) were observed in the hospital-acquired peritonitis group compared to the community-acquired peritonitis group, respectively.
CONCLUSIONS
Despite having lower peritoneal dialysis effluent leucocyte counts at the time of diagnosis, patients with hospital-acquired peritonitis had poorer outcomes, including lower rates of complete cure, higher rates of refractory peritonitis and higher rates of all-cause mortality within 30 days of diagnosis, compared to those with community-acquired peritonitis.
Topics: Adult; Humans; Retrospective Studies; Peritoneal Dialysis; Peritonitis; Peritoneum; Hospitals
PubMed: 36913080
DOI: 10.1007/s40620-023-01597-w