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Artificial Organs Jul 2023Following the first wave of COVID-19 there have been several variants. We wished to review the number and severity of infections with the different variants in a... (Review)
Review
INTRODUCTION
Following the first wave of COVID-19 there have been several variants. We wished to review the number and severity of infections with the different variants in a population of hemodialysis (HD) and peritoneal dialysis (PD) patients.
METHODS
We reviewed the outcomes and results in HD and PD patients testing positive for COVID-19 between March 2020 and August 2022.
RESULTS
Seven hundred and ninety-five cases of COVID-19 were recorded in 710 dialysis patients. More HD patients than PD contracted wild type (21.4% vs. 6.8%), delta (23.3% vs 6.3%), and omicron (27.7% vs. 14.7%), all p < 0.01, but no difference with alpha (4.6% vs. 6.3%) or beta variants (5.7% vs. 6.85%). Hospitalization and death were greatest for alpha followed by wild type, beta, delta, and omicron (60.6% vs. 57% vs. 47.5% vs. 21.2% vs. 19.3%), respectively, p < 0.001. C reactive protein progressively increased from outpatient management to hospitalization to hospitalization with critical care or death (14 (4-30) vs. 41 (18-101) vs. 94 (47-168) mg/L, p < 0.001. Despite previous infection and vaccination 85 (12%) patients had two or more infections with COVID-19.
CONCLUSION
Disease severity declined and survival improved as the virus mutated from wild-type and alpha to beta, delta, and omicron variants. Whether this related to reduction in viral virulence, vaccination, natural acquired immunity, or introduction of pharmacological treatments remains to be determined. Government lockdowns and enhanced infection control measures reduced the percentage of HD patients contracting alpha and beta variants to that of PD. Vaccination and prior infection did not prevent reinfection.
Topics: Humans; Kidney Failure, Chronic; COVID-19; Communicable Disease Control; SARS-CoV-2; Renal Dialysis; Peritoneal Dialysis
PubMed: 36949657
DOI: 10.1111/aor.14526 -
EBioMedicine Mar 2024Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene...
BACKGROUND
Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) and its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, and inflammation in macrophages. Here we explore whether itaconate regulates phagocytosis.
METHODS
Phagocytosis of macrophages was investigated by time-lapse video recording, flow cytometry, and immunofluorescence staining in macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing and ChIP-sequencing assays were used to explore the underlying mechanisms. The effects of Irg1/itaconate axis on the prognosis of intracerebral hemorrhagic stroke (ICH) and peritonitis was observed in transgenic (Irg1; Cx3cr1, cKO) mice or control mice in vivo.
FINDINGS
In a mouse model of ICH, depletion of Irg1 in macrophage/microglia decreased its phagocytosis of erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p < 0.05). Administration of sodium itaconate/4-octyl itaconate (4-OI) promoted macrophage phagocytosis (n = 7 animals/group, p < 0.05). In addition, in a mouse model of peritonitis, Irg1 deficiency in macrophages also inhibited phagocytosis of Staphylococcus aureus (n = 5 animals/group, p < 0.05) and aggravated outcomes (n = 9 animals/group, p < 0.05). Mechanistically, 4-OI alkylated cysteine 155 on the Kelch-like ECH-associated protein 1 (Keap1), consequent in nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and transcriptional activation of Cd36 gene. Blocking the function of CD36 completely abolished the phagocytosis-promoting effects of Irg1/itaconate axis in vitro and in vivo.
INTERPRETATION
Our findings provide a potential therapeutic target for phagocytosis-deficiency disorders, supporting further development towards clinical application for the benefit of stroke and peritonitis patients.
FUNDING
The National Natural Science Foundation of China (32070735, 82371321 to Q. Li, 82271240 to F. Yang) and the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ202010025033 to Q. Li).
Topics: Humans; Mice; Animals; Kelch-Like ECH-Associated Protein 1; Hemorrhagic Stroke; NF-E2-Related Factor 2; Macrophages; Peritonitis; Phagocytosis; Prognosis; Hydro-Lyases; Succinates
PubMed: 38324982
DOI: 10.1016/j.ebiom.2024.104993 -
PLoS Pathogens Oct 2023Even though gammaherpesvirus and parasitic infections are endemic in parts of the world, there is a lack of understanding about the outcome of coinfection. In humans,...
Even though gammaherpesvirus and parasitic infections are endemic in parts of the world, there is a lack of understanding about the outcome of coinfection. In humans, coinfections usually occur sequentially, with fluctuating order and timing in different hosts. However, experimental studies in mice generally do not address the variables of order and timing of coinfections. We sought to examine the variable of coinfection order in a system of gammaherpesvirus-helminth coinfection. Our previous work demonstrated that infection with the intestinal parasite, Heligmosomoides polygyrus, induced transient reactivation from latency of murine gammaherpesvirus-68 (MHV68). In this report, we reverse the order of coinfection, infecting with H. polygyrus first, followed by MHV68, and examined the effects of preexisting parasite infection on MHV68 acute and latent infection. We found that preexisting parasite infection increased the propensity of MHV68 to reactivate from latency. However, when we examined the mechanism for reactivation, we found that preexisting parasite infection increased the ability of MHV68 to reactivate in a vitamin A dependent manner, a distinct mechanism to what we found previously with parasite-induced reactivation after latency establishment. We determined that H. polygyrus infection increased both acute and latent MHV68 infection in a population of tissue resident macrophages, called large peritoneal macrophages. We demonstrate that this population of macrophages and vitamin A are required for increased acute and latent infection during parasite coinfection.
Topics: Humans; Animals; Mice; Virus Activation; Coinfection; Virus Latency; Vitamin A; B-Lymphocytes; Herpesviridae Infections; Gammaherpesvirinae; Macrophages; Latent Infection; Helminths; Parasitic Diseases; Mice, Inbred C57BL
PubMed: 37847677
DOI: 10.1371/journal.ppat.1011691 -
Seminars in Dialysis 2024Patients with kidney failure who require kidney replacement therapy (KRT) have been increasing globally. Home-based therapies, such as peritoneal dialysis (PD), allow... (Review)
Review
Patients with kidney failure who require kidney replacement therapy (KRT) have been increasing globally. Home-based therapies, such as peritoneal dialysis (PD), allow patients to undergo KRT in the home environment, alleviating treatment costs, patient transport, and hospital admission. Peritoneal dialysis-related peritonitis is still the most frequent complication of PD and is often related to technique failure, which can result in PD failure, transfer to hemodialysis, or mortality. The cause of technique failure is multifactorial, and a portion of technique failure is due to underlying physical or cognitive disabilities. There are several connection devices that have been developed to reduce CAPD-related peritonitis. These connection devices are reviewed in this article.
Topics: Humans; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Renal Dialysis
PubMed: 36117288
DOI: 10.1111/sdi.13123 -
Tropical Animal Health and Production Oct 2023Gallibacterium anatis (G. anatis), a member of the Pasteurellaceae family, normally inhabits the upper respiratory and lower genital tracts of poultry. However, under... (Review)
Review
Gallibacterium anatis (G. anatis), a member of the Pasteurellaceae family, normally inhabits the upper respiratory and lower genital tracts of poultry. However, under certain circumstances of immunosuppression, co-infection (especially with Escherichia coli or Mycoplasma), or various stressors, G. anatis caused respiratory, reproductive, and systemic diseases. Infection with G. anatis has emerged in different countries worldwide. The bacterium affects mainly chickens; however, other species of domestic and wild birds may get infected. Horizontal, vertical, and venereal routes of G. anatis infection have been reported. The pathogenicity of G. anatis is principally related to the presence of some essential virulence factors such as Gallibacterium toxin A, fimbriae, haemagglutinin, outer membrane vesicles, capsule, biofilms, and protease. The clinical picture of G. anatis infection is mainly represented as tracheitis, oophoritis, salpingitis, and peritonitis, while other lesions may be noted in cases of concomitant infection. Control of such infection depends mainly on applying biosecurity measures and vaccination. The antimicrobial sensitivity test is necessary for the correct treatment of G. anatis. However, the development of multiple drug resistance is common. This review article sheds light on G. anatis regarding history, susceptibility, dissemination, virulence factors, pathogenesis, clinical picture, diagnosis, and control measures.
Topics: Female; Animals; Poultry; Chickens; Pasteurellaceae Infections; Pasteurellaceae; Virulence Factors; Escherichia coli; Poultry Diseases
PubMed: 37889324
DOI: 10.1007/s11250-023-03796-w -
Emerging Infectious Diseases Aug 2023Mycolicibacterium neoaurum is a rapidly growing mycobacterium and an emerging cause of human infections. M. neoaurum infections are uncommon but likely underreported,... (Review)
Review
Mycolicibacterium neoaurum is a rapidly growing mycobacterium and an emerging cause of human infections. M. neoaurum infections are uncommon but likely underreported, and our understanding of the disease spectrum and optimum management is incomplete. We summarize demographic and clinical characteristics of a case of catheter-related M. neoaurum bacteremia in a child with leukemia and those of 36 previously reported episodes of M. neoaurum infection. Most infections occurred in young to middle-aged adults with serious underlying medical conditions and commonly involved medical devices. Overall, infections were not associated with severe illness or death. In contrast to other mycobacteria species, M. neoaurum was generally susceptible to multiple antimicrobial drugs and responded promptly to treatment, and infections were associated with good outcomes after relatively short therapy duration and device removal. Delays in identification and susceptibility testing were common. We recommend using combination antimicrobial drug therapy and removal of infected devices to eradicate infection.
Topics: Child; Humans; Middle Aged; Cross Infection; Delivery of Health Care; Mycobacteriaceae; Mycobacterium; Mycobacterium Infections; Young Adult
PubMed: 37486155
DOI: 10.3201/eid2908.230007 -
Journal of Obstetrics and Gynaecology... Feb 2024
Topics: Female; Humans; Tuberculosis; Abdomen; Ovarian Neoplasms; Diagnosis, Differential; Peritonitis, Tuberculous
PubMed: 37598884
DOI: 10.1016/j.jogc.2023.102193 -
Journal of Clinical Medicine Jun 2023Peritoneal fibrosis is the final process of progressive changes in the peritoneal membrane due to chronic inflammation and infection. It is one of the main causes of... (Review)
Review
Peritoneal fibrosis is the final process of progressive changes in the peritoneal membrane due to chronic inflammation and infection. It is one of the main causes of discontinuation of peritoneal dialysis (PD), apart from peritonitis and cardiovascular complications. Over time, morphological changes occur in the peritoneal membranes of patients who use PD. Of those are mesothelial-to-mesenchymal transition (MMT), neoangiogenesis, sub-mesothelial fibrosis, and hyalinizing vasculopathy. Several key molecules are involved in the complex pathophysiology of peritoneal fibrosis, including advanced glycosylation end products (AGEs), transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF). This narrative review will first discuss the physiology of the peritoneum and PD. Next, the multifaceted pathophysiology of peritoneal fibrosis, including the effects of hyperglycemia and diabetes mellitus on the peritoneal membrane, and the promising biomarkers of peritoneal fibrosis will be reviewed. Finally, the current and future management of peritoneal fibrosis will be discussed, including the potential benefits of new-generation glucose-lowering medications to prevent or slow down the progression of peritoneal fibrosis.
PubMed: 37445436
DOI: 10.3390/jcm12134401 -
Frontiers in Immunology 2023The recent discovery of TAK981(Subasumstat), the first-in-class selective inhibitor of SUMOylation, enables new immune treatments. TAK981 is already in clinical trials...
INTRODUCTION
The recent discovery of TAK981(Subasumstat), the first-in-class selective inhibitor of SUMOylation, enables new immune treatments. TAK981 is already in clinical trials to potentiate immunotherapy in metastatic tumors and hematologic malignancies. Cancer patients have more than ten times higher risk of infections, but the effects of TAK981 in sepsis are unknown and previous studies on SUMO in infections are conflicting.
METHODS
We used TAK981 in two sepsis models; polymicrobial peritonitis (CLP) and LPS endotoxemia. Splenectomy was done in both models to study the role of spleen. Western blotting of SUMO-conjugated proteins in spleen lysates was done. Global SUMO1 and SUMO3 knockout mice were used to study the specific SUMO regulation of inflammation in LPS endotoxemia. Splenocytes adoptive transfer was done from SUMO knockouts to wild type mice to study the role of spleen SUMOylation in experimental sepsis.
RESULTS AND DISCUSSION
Here, we report that inhibition of SUMOylation with TAK981 improved survival in mild polymicrobial peritonitis by enhancing innate immune responses and peritoneal bacterial clearance. Thus, we focused on the effects of TAK981 on the immune responses to bacterial endotoxin, showing that TAK981 enhanced early TNFα production but did not affect the resolution of inflammation. Splenectomy decreased serum TNFα levels by nearly 60% and TAK981-induced TNFα responses. In the spleen, endotoxemia induced a distinct temporal and substrate specificity for SUMO1 and SUMO2/3, and both were inhibited by TAK981. Global genetic depletion of SUMO1, but not SUMO3, enhanced TNFα production and metabolic acidosis. The transfer of SUMO1-null, but not wild-type, splenocytes into splenectomized wild-type mice exacerbated TNFα production and metabolic acidosis in endotoxemia.
CONCLUSION
These results suggest that specific regulation of splenic SUMO1 can modulate immune and metabolic responses to bacterial infection.
Topics: Animals; Mice; Endotoxemia; Lipopolysaccharides; Mice, Knockout; Peritonitis; Small Ubiquitin-Related Modifier Proteins; Spleen; Tumor Necrosis Factor-alpha; SUMO-1 Protein
PubMed: 37520526
DOI: 10.3389/fimmu.2023.1200939 -
Nephrology (Carlton, Vic.) Aug 2023Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the...
BACKGROUND
Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes.
METHODS
We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis.
RESULTS
Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin.
CONCLUSION
Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients.
Topics: Humans; Thailand; Peritoneal Dialysis; Renal Dialysis; Constipation; Peritonitis; Kidney Failure, Chronic
PubMed: 37534844
DOI: 10.1111/nep.14224