-
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 -
The Pediatric Infectious Disease Journal Oct 2023In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of...
BACKGROUND
In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of this study was to determine the prevalence and characterize the types of immunodeficiencies in children presenting with IPD.
METHODS
Multicenter prospective audit following the introduction of routinely recommended immunological screening in children presenting with IPD. The minimum immunological evaluation comprised a full blood examination and film, serum immunoglobulins (IgG, IgA and IgM), complement levels and function. Included participants were children in whom Streptococcus pneumoniae was isolated from a normally sterile site (cerebrospinal fluid, pleura, peritoneum and synovium). If isolated from blood, features of sepsis needed to be present. Children with predisposing factors for IPD (nephrotic syndrome, anatomical defect or malignancy) were excluded.
RESULTS
Overall, there were 379 episodes of IPD of which 313 (83%) were eligible for inclusion and 143/313 (46%) had an immunologic evaluation. Of these, 17/143 (12%) were diagnosed with a clinically significant abnormality: hypogammaglobulinemia (n = 4), IgA deficiency (n = 3), common variable immunodeficiency (n = 2), asplenia (n = 2), specific antibody deficiency (n = 2), incontinentia pigmenti with immunologic dysfunction (n = 1), alternative complement deficiency (n = 1), complement factor H deficiency (n = 1) and congenital disorder of glycosylation (n = 1). The number needed to investigate to identify 1 child presenting with IPD with an immunologic abnormality was 7 for children under 2 years and 9 for those 2 years old and over.
CONCLUSIONS
This study supports the routine immune evaluation of children presenting with IPD of any age, with consideration of referral to a pediatric immunologist.
Topics: Child; Humans; Infant; Child, Preschool; Prospective Studies; Pneumococcal Infections; Streptococcus pneumoniae; Sepsis; Immunologic Deficiency Syndromes; Pneumococcal Vaccines; Incidence
PubMed: 37463351
DOI: 10.1097/INF.0000000000004004 -
Current Protocols Mar 2024Human sepsis is a complex disease that manifests with a diverse range of phenotypes and inherent variability among individuals, making it hard to develop a comprehensive...
Human sepsis is a complex disease that manifests with a diverse range of phenotypes and inherent variability among individuals, making it hard to develop a comprehensive animal model. Despite this difficulty, numerous models have been developed that capture many key aspects of human sepsis. The robustness of these models is vital for conducting pre-clinical studies to test and develop potential therapeutics. In this article, we describe four different models of murine sepsis that can be used to address different scientific questions relevant to the pathology and immune response during and after a septic event. Basic Protocol 1 details a non-synchronous cecal ligation and puncture (CLP) model of sepsis, where mice are subjected to polymicrobial exposure through surgery at different time points within 2 weeks. This variation in sepsis onset establishes each mouse at a different state of inflammation and cytokine levels that mimics the variability observed in humans when they present in the clinic. This model is ideal for studying the long-term impact of sepsis on the host. Basic Protocol 2 is also a type of polymicrobial sepsis, where injection of a specific amount of cecal slurry from a donor mouse into the peritoneum of recipient mice establishes immediate inflammation and sepsis without any need for surgery. Basic Protocol 3 describes infecting mice with a defined gram-positive or -negative bacterial strain to model a subset of sepsis observed in humans infected with a single pathogen. Basic Protocol 4 describes administering LPS to induce sterile endotoxemia. This form of sepsis is observed in humans exposed to bacterial toxins from the environment. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Non-synchronous cecal ligation and puncture Basic Protocol 2: Cecal slurry model of murine sepsis Basic Protocol 3: Monomicrobial model of murine sepsis Basic Protocol 4: LPS model of murine sepsis.
Topics: Humans; Animals; Mice; Lipopolysaccharides; Disease Models, Animal; Sepsis; Ambulatory Care Facilities; Inflammation
PubMed: 38439603
DOI: 10.1002/cpz1.997 -
Peritoneal Dialysis International :... Nov 2023To optimise antimicrobial administration in patients with peritoneal dialysis (PD)-related peritonitis, healthcare providers need literature-based information to develop... (Review)
Review
To optimise antimicrobial administration in patients with peritoneal dialysis (PD)-related peritonitis, healthcare providers need literature-based information to develop patient-centred pharmacotherapeutic plans. Traditional PD solutions promote osmosis using dextrose or icodextrin with a lactate buffer. Newer PD solutions have modified the osmotic vehicle and buffer. Knowledge of antimicrobial compatibility and stability with newer PD solutions will assist with determining the route of antimicrobial administration as compatible and stable solutions could be delivered directly to the peritoneum using intraperitoneal administration. This review updates the compatibility and stability of antimicrobial additives in newer PD solutions for PD-related peritonitis.
Topics: Humans; Peritoneal Dialysis; Dialysis Solutions; Peritonitis; Anti-Infective Agents; Lactic Acid; Glucose
PubMed: 37728078
DOI: 10.1177/08968608231196034 -
Frontiers in Immunology 2023American trypanosomiasis, or Chagas disease, is caused by the protozoan parasite and is characterized by the presence of cardiac or gastrointestinal symptoms in a large...
Extracellular vesicles of and immune complexes they form with sialylated and non-sialylated IgGs increase small peritoneal macrophage subpopulation and elicit different cytokines profiles.
American trypanosomiasis, or Chagas disease, is caused by the protozoan parasite and is characterized by the presence of cardiac or gastrointestinal symptoms in a large number of patients during the chronic phase of the disease. Although the origin of the symptoms is not clear, several mechanisms have been described involving factors related to and the host immune response. In this sense, the extracellular vesicles (EVs) secreted by the parasite and the immune complexes (ICs) formed after their recognition by host IgGs (EVs-IgGs) may play an important role in the immune response during infection. The aim of the present work is to elucidate the modulation of the immune response exerted by EVs and the ICs they form by analyzing the variation in the subpopulations of small and large peritoneal macrophages after intraperitoneal inoculation in mice and to evaluate the role of the sialylation of the host IgGs in this immunomodulation. Both macrophage subpopulations were purified and subjected to cytokine expression analysis by RT-qPCR. The results showed an increase in the small peritoneal macrophage subpopulation after intraperitoneal injection of parasite EVs, but a greater increase in this subpopulation was observed when sialylated and non-sialylated ICs were injected, which was similar to inoculation with the trypomastigote stage of the parasite. The cytokine expression results showed the ability of both subpopulations to express inflammatory and non-inflammatory cytokines. These results suggest the role of free EVs in the acute phase of the disease and the possible role of immune complexes in the immune response in the chronic phase of the disease, when the levels of antibodies against the parasite allow the formation of immune complexes. The differential expression of interleukins showed after the inoculation of immune complexes formed with sialylated and non-sialylated IgGs and the interleukins expression induced by EVs, demonstrates that the IgG glycosilation is involved in the type of immune response that dominates in each of the phases of the Chagas disease.
Topics: Animals; Mice; Trypanosoma cruzi; Antigen-Antibody Complex; Macrophages, Peritoneal; Chagas Disease; Cytokines; Extracellular Vesicles
PubMed: 37600828
DOI: 10.3389/fimmu.2023.1215913 -
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 -
International Urology and Nephrology Aug 2023There were discrete outbreaks of SARS-CoV-2 infection in 2021 (Delta wave) and 2022 (Omicron wave) in Singapore, which affected patients receiving peritoneal dialysis...
INTRODUCTION
There were discrete outbreaks of SARS-CoV-2 infection in 2021 (Delta wave) and 2022 (Omicron wave) in Singapore, which affected patients receiving peritoneal dialysis (PD).
METHODS
This study included all PD patients with COVID-19 infection from a single center between October 2021 and March 2022. The clinical presentation, management and outcomes of patients during the Delta and Omicron outbreaks were compared.
RESULTS
A total of 44 PD patients developed SARS-CoV-2 infection (23 during the Delta wave and 21 during the Omicron wave): median age 66 (60.5-68.5) years, male (63.6%), Chinese ethnic (77.3%), diabetes mellitus (56.8%), and cardiovascular disease (45.5%). Approximately, 93.2% received two doses of the mRNA COVID-19 vaccine. Cough (81.8%) and fever (54.5%) were common presenting symptoms. Chest radiography showed ground glass opacity in 23.5% of patients, consolidation in 55.6%, and bilateral lung involvement in 33.3%. Eleven patients (25.6%) received antiviral therapy (Remdesivir), 7 (16.3%) received steroid, and 4 (9.3%) received monoclonal antibodies. Patients infected during the Delta wave were more likely to be hospitalized (73.9 vs 14.3%; p < 0.001) and receive antiviral therapy (39.1 vs 10.0%; p = 0.03) than those during the Omicron wave. The overall mortality rate was 11.4%, with significantly higher mortality during the Delta wave than during the Omicron wave (21.7 vs 0%; p = 0.03).
CONCLUSIONS
The mortality rate was high among infected PD patients during Delta wave of COVID-19 infection. However, during the Omicron wave, most infected patients were treated in the community with favorable outcomes.
Topics: Aged; Humans; Male; Antiviral Agents; COVID-19; COVID-19 Vaccines; Peritoneal Dialysis; SARS-CoV-2
PubMed: 36820945
DOI: 10.1007/s11255-023-03496-2 -
Frontiers in Immunology 2023Syphilis, a sexually transmitted infection caused by the spirochete (), is resurging globally. 's repertoire of outer membrane proteins (OMPs) includes BamA (β-barrel...
INTRODUCTION
Syphilis, a sexually transmitted infection caused by the spirochete (), is resurging globally. 's repertoire of outer membrane proteins (OMPs) includes BamA (β-barrel assembly machinery subunit A/TP0326), a bipartite protein consisting of a 16-stranded β-barrel with nine extracellular loops (ECLs) and five periplasmic POTRA (polypeptide transport-associated) domains. BamA ECL4 antisera promotes internalization of by rabbit peritoneal macrophages.
METHODS
Three overlapping BamA ECL4 peptides and a two-stage, phage display strategy, termed "Epivolve" (for epitope evolution) were employed to generate single-chain variable fragments (scFvs). Additionally, antisera generated by immunizing mice and rabbits with BamA ECL4 displayed by a thioredoxin scaffold (Trx). MAbs and antisera reactivities were evaluated by immunoblotting and ELISA. A comparison of murine and rabbit opsonophagocytosis assays was conducted to evaluate the functional ability of the Abs (, opsonization) and validate the mouse assay. Sera from -infected mice (MSS) and rabbits (IRS) were evaluated for ECL4-specific Abs using Trx and overlapping ECL4 peptides in immunoblotting and ELISA assays.
RESULTS
Each of the five mAbs demonstrated reactivity by immunoblotting and ELISA to nanogram amounts of Trx. One mAb, containing a unique amino acid sequence in both the light and heavy chains, showed activity in the murine opsonophagocytosis assay. Mice and rabbits hyperimmunized with Trx produced opsonic antisera that strongly recognized the ECL presented in a heterologous scaffold and overlapping ECL4 peptides, including S2. In contrast, Abs generated during infection of mice and rabbits poorly recognized the peptides, indicating that S2 contains a subdominant epitope.
DISCUSSION
Epivolve produced mAbs target subdominant opsonic epitopes in BamA ECL4, a top syphilis vaccine candidate. The murine opsonophagocytosis assay can serve as an alternative model to investigate the opsonic potential of vaccinogens. Detailed characterization of BamA ECL4-specific Abs provided a means to dissect Ab responses elicited by infection.
Topics: Mice; Animals; Rabbits; Treponema pallidum; Antibodies, Monoclonal; Syphilis; Immune Sera; Bacteriophages; Epitopes
PubMed: 37675118
DOI: 10.3389/fimmu.2023.1222267 -
Indian Journal of Pediatrics Mar 2024Development of ascites in children with chronic liver disease is the most common form of decompensation. It is associated with a poor prognosis and increased risk of... (Review)
Review
Development of ascites in children with chronic liver disease is the most common form of decompensation. It is associated with a poor prognosis and increased risk of mortality. A diagnostic paracentesis should be performed in liver disease patients with- new-onset ascites, at the beginning of each hospital admission and when ascitic fluid infection (AFI) is suspected. The routine analysis includes cell count with differential, bacterial culture, ascitic fluid total protein and albumin. A serum albumin-ascitic fluid albumin gradient of ≥1.1 g/dL confirms the diagnosis of portal hypertension. Ascites has been reported in children with non-cirrhotic liver disease like acute viral hepatitis, acute liver failure and extrahepatic portal venous obstruction. The main steps in management of cirrhotic ascites include dietary sodium restriction, diuretics and large-volume paracentesis. Sodium should be restricted to maximum of 2 mEq/kg/d (max 90 mEq/d) of sodium/day. Oral diuretic therapy comprises of aldosterone antagonists (e.g., spironolactone) with or without loop-diuretics (e.g., furosemide). Once the ascites is mobilized, the diuretics should be gradually tapered to the minimum effective dosage. Tense ascites should be managed with a large-volume paracentesis (LVP) preferably with albumin infusion. Therapeutic options for refractory ascites include recurrent LVP, transjugular intrahepatic porto-systemic shunt and liver transplantation. AFI (fluid neutrophil count ≥250/mm) is an important complication, and requires prompt antibiotic therapy. Hyponatremia, acute kidney injury, hepatic hydrothorax and hernias are the other complications.
Topics: Child; Humans; Ascites; Peritonitis; Diuretics; Paracentesis; Hypertension, Portal; Serum Albumin; Sodium; Liver Cirrhosis
PubMed: 37310583
DOI: 10.1007/s12098-023-04596-8 -
Journal of Renal Care Dec 2023Peritonitis is a common cause of hospitalisation and death among patients undergoing peritoneal dialysis. Periodic retraining is recommended to prevent peritonitis,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Peritonitis is a common cause of hospitalisation and death among patients undergoing peritoneal dialysis. Periodic retraining is recommended to prevent peritonitis, especially in older adults.
OBJECTIVES
We evaluated the effectiveness of a retraining programme for reducing peritonitis and exit site infection rates in older adults on peritoneal dialysis. The cost-benefit ratio was also calculated.
DESIGN
A two-arm prospective randomised controlled trial.
PARTICIPANTS
One hundred and thirty patients aged 55 years or older were recruited. Participants were randomly assigned to the intervention or control group. While both groups received usual care, the intervention group received a retraining programme (a knowledge and practical assessment and a one-on-one retraining session) 90 days after starting home-based continuous ambulatory peritoneal dialysis therapy.
MEASUREMENTS
The outcomes included peritonitis rate, exit site infection rate and direct medical costs at 180, 270, and 360 days after starting home-based continuous ambulatory peritoneal dialysis therapy.
RESULTS
No significant differences were found in the baseline characteristics between groups. The peritonitis rates were 0.11 episodes per patient-year in the intervention group versus 0.13 in the control group. The incidence of exit site infection was 20.0% in the intervention group and 12.3% in the control group. The cost-benefit ratio of retraining was 1:9.6. None of the results were statistically significant.
CONCLUSIONS
The absence of statistical significance may be partly explained by the premature termination of the study. Large-scale multi-centre trials are warranted to examine the effectiveness of retraining. The timing and long-term effects of retraining also need to be examined.
Topics: Humans; Aged; Prospective Studies; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Cost-Benefit Analysis
PubMed: 36463502
DOI: 10.1111/jorc.12450