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Nature Communications May 2024Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for...
Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that CD5L's important features include its ability to enhance neutrophil recruitment and activation by increasing circulating levels of CXCL1, and to promote neutrophil phagocytosis. CD5L-deficient mice exhibit impaired neutrophil recruitment and compromised bacterial control, rendering them susceptible to attenuated CLP. CD5L peritoneal cells from mice subjected to medium-grade CLP exhibit a heightened pro-inflammatory transcriptional profile, reflecting a loss of control of the immune response to the infection. Intravenous administration of recombinant CD5L (rCD5L) in immunocompetent C57BL/6 wild-type (WT) mice significantly ameliorates measures of disease in the setting of high-grade CLP-induced sepsis. Furthermore, rCD5L lowers endotoxin and damage-associated molecular pattern (DAMP) levels, and protects WT mice from LPS-induced endotoxic shock. These findings warrant the investigation of rCD5L as a possible treatment for sepsis in humans.
Topics: Animals; Sepsis; Mice, Inbred C57BL; Mice; Neutrophils; Mice, Knockout; Phagocytosis; Chemokine CXCL1; Disease Models, Animal; Male; Neutrophil Infiltration; Cecum; Recombinant Proteins; Humans; Pore Forming Cytotoxic Proteins; Ligation; Lipopolysaccharides; Shock, Septic
PubMed: 38750020
DOI: 10.1038/s41467-024-48360-8 -
Scientific Reports Oct 2023Non-tuberculosis mycobacterial (NTM) diseases are steadily increasing in prevalence and mortality worldwide. Mycobacterium avium and M. intracellulare, the two major...
Non-tuberculosis mycobacterial (NTM) diseases are steadily increasing in prevalence and mortality worldwide. Mycobacterium avium and M. intracellulare, the two major pathogens of NTM diseases, are resistant to antibiotics, and chlorine, necessitating their capacity to survive in natural environments (e.g. soil and rivers) and disinfected municipal water. They can also form biofilms on artificial surfaces to provide a protective barrier and habitat for bacilli, which can cause refractory systemic disseminated NTM disease. Therefore, preventing biofilm formation by these pathogens is crucial; however, not many in vivo experimental systems and studies on NTM biofilm infection are available. This study develops a mouse model of catheter-associated systemic disseminated disease caused by M. intracellulare that reproduces the pathophysiology of catheter-associated infections observed in patients undergoing peritoneal dialysis. In addition, the bioluminescence system enabled noninvasive visualization of the amount and distribution of bacilli in vivo and conveniently examine the efficacy of antimicrobials. Furthermore, the cellulose-based biofilms, which were extensively formed in the tissue surrounding the catheter insertion site, reduced drug therapy effectiveness. Overall, this study provides insights into the cause of the drug resistance of NTM and may guide the development of new therapies for NTM diseases.
Topics: Humans; Mice; Animals; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Mice, Inbred Strains; Catheters; Biofilms; Bacillus
PubMed: 37816786
DOI: 10.1038/s41598-023-44403-0 -
BMC Cancer Sep 2023Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard treatment for pseudomyxoma peritonei (PMP). It can significantly...
BACKGROUND
Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard treatment for pseudomyxoma peritonei (PMP). It can significantly prolong the survival of patients, but at the same time may increase the risk of postoperative infection.
METHOD
Patients with PMP who underwent CRS + HIPEC at our center were retrospectively analyzed. According to PMP patients, basic clinical data and relevant information of postoperative infection, we analyzed the common sites of postoperative infection, results of microbial culture and the antibiotics sensitivity. Univariate and multivariate analysis were performed to explore infection-related risk factors.
RESULT
Among the 482 patients with PMP, 82 (17.0%) patients were infected after CRS + HIPEC. The most common postoperative infection was central venous catheter (CVC) infection (8.1%), followed by abdominal-pelvic infection (5.2%). There were 29 kinds of microbes isolated from the culture (the most common was Staphylococcus epidermidis), including 13 kinds of Gram-positive bacteria, 12 kinds of Gram-negative bacteria, and 4 kinds of funguses. All the antibiotics sensitivity results showed that the most sensitive antibiotics were vancomycin to Gram-positive bacteria (98.4%), levofloxacin to Gram-negative bacteria (68.5%), and fluconazole to fungus (83.3%). Univariate and multivariate analysis revealed the infection independent risk factors as follow: intraoperative blood loss ≥ 350 mL (P = 0.019), ascites volume ≥ 300 mL (P = 0.008).
CONCLUSION
PMP patients may have increased infection risk after CRS + HIPEC, especially CVC, abdominal-pelvic and pulmonary infections. The microbial spectrum and antibiotics sensitivity results could help clinicians to take prompt prophylactic and therapeutic approaches against postoperative infection for PMP patients.
Topics: Humans; Hyperthermic Intraperitoneal Chemotherapy; Cytoreduction Surgical Procedures; Pseudomyxoma Peritonei; Retrospective Studies; Anti-Bacterial Agents; Peritoneal Neoplasms
PubMed: 37752468
DOI: 10.1186/s12885-023-11404-1 -
Antiviral Research Aug 2023COVID-19 causes significant mortality during the recent pandemic. Data regarding the effectiveness of Paxlovid on COVID-19 patients with chronic kidney disease (CKD,...
BACKGROUND
COVID-19 causes significant mortality during the recent pandemic. Data regarding the effectiveness of Paxlovid on COVID-19 patients with chronic kidney disease (CKD, eGFR <90 ml/min) are limited.
METHODS
A retrospective cohort study was performed on the clinical data of the hospitalized adult patients with confirmed COVID-19 infection collected at Renji Hospital from April 7, 2022 to June 21, 2022. The association of Paxlovid treatment with early (within 5 days post diagnosis) or late (5 days or later post diagnosis) initiation time with clinical outcomes was assessed by Cox proportional hazards regression model with time-dependent covariates.
RESULT
1279 of 2387 enrollees were included in the study. Patients with early initiation of Paxlovid had a lower all-cause death rate compared to those with late initiation or without Paxlovid treatment (P = 0.046). For the CKD patients with Charlson comorbidity index (CCI) > 7, the early initiation of Paxlovid was associated with a lower all-cause death rate compared to the later initiation or the lack of Paxlovid treatment (P = 0.041). Cox regression analyses revealed that eGFR (HR 4.21 [95%, CI 1.62-10.99]), Paxlovid treatment (0.32 [0.13-0.77]), CCI (4.32 [1.64-11.40]), ICU admission (2.65 [1.09-6.49]), hsCRP (3.88 [1.46-7.80]), chronic liver disease (4.02 [1.09-14.85]) were the independent risk factors for all-cause death for CKD patients after adjusting for demographics and biochemical indexes.
CONCLUSIONS
All-cause death, invasive ventilation, and ICU admission were all significantly lowered by an early initiation of Paxlovid treatment in COVID-19 patients with severe CKD.
Topics: Adult; Humans; COVID-19; Retrospective Studies; Renal Insufficiency, Chronic; Risk Factors
PubMed: 37369283
DOI: 10.1016/j.antiviral.2023.105659 -
Critical Care (London, England) Nov 2023Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments....
BACKGROUND
Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-D-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC.
METHODS
This prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell beta-D-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements.
RESULTS
Between 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54-72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5-1578.0] pg/ml) compared to non-IAC patients (133 [16.0-831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0-9.0] pg/ml) than in non-IAC patients (3 [3.0-3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0-211.0] pg/ml) than in non-IAC patients (50 [23.0-141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%.
CONCLUSION
In critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure.
TRIAL REGISTRATION
The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).
Topics: Humans; Male; Middle Aged; Aged; Female; Prospective Studies; Glucans; Critical Illness; Candidiasis; Antifungal Agents; Intraabdominal Infections; Peritonitis; beta-Glucans; Sensitivity and Specificity
PubMed: 38037130
DOI: 10.1186/s13054-023-04761-7 -
Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis.Stem Cell Research & Therapy Dec 2023The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it...
BACKGROUND
The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis.
METHODS
We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 10 cells/kg or 4 × 10 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity.
RESULTS
One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-β in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity.
CONCLUSIONS
Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.
Topics: Humans; Animals; Swine; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Mesenchymal Stem Cells; Peritonitis; Sepsis; Anti-Bacterial Agents
PubMed: 38087374
DOI: 10.1186/s13287-023-03588-x -
Internal Medicine (Tokyo, Japan) Feb 2024
Topics: Humans; Female; Ascites; Peritoneum; Tuberculosis; Ovarian Neoplasms; Peritonitis, Tuberculous
PubMed: 37344427
DOI: 10.2169/internalmedicine.2013-23 -
Materia Socio-medica 2024Infection causes cirrhosis to decompensate, affecting liver function and resulting in several complications, including esophageal variceal hemorrhage, hepatic...
BACKGROUND
Infection causes cirrhosis to decompensate, affecting liver function and resulting in several complications, including esophageal variceal hemorrhage, hepatic encephalopathy, and hepatorenal syndrome. Objective: This study aimed to identify the prevalence, essential features, and related factors of bacterial infection among patients with cirrhosis in Vietnam.
METHODS
This retrospective study included 317 patients diagnosed with cirrhosis, who were divided into two groups: group 1 including 125 patients with bacterial infection and group 2 including 192 patients without bacterial infection. Infection was diagnosed on the basis of its localization.
RESULTS
Spontaneous bacterial peritonitis (SBP; 31.2%) and pneumonia (28.8%) were the most common infections identified. The procalcitonin (PCT) level had a strong diagnostic value with an area under the curve value of 0.868. The most common type of gram-negative bacteria was Escherichia coli, while the gram-positive bacteria seen were Staphylococcus, Enterococcus, and Streptococcus among the patients with infection. In the logistic regression analysis, Child-Pugh class B and C (p<0.001, OR=4.14, CI=1.90-9.03; OR=4.76, CI=2.03-11.16, respectively) and the presence of acute kidney injury (p=0.009, OR=2.57, CI=1.27-5.22) and gastrointestinal hemorrhage (p=0.035, OR=0.39, CI=0.16-0.94) significantly differed between the groups.
CONCLUSION
The most prevalent type of bacterial infection in patients with cirrhosis is SBP, with gram-negative bacteria being the most common cause. The PCT level is useful in identifying infection in patients with cirrhosis. Decompensated cirrhosis is linked to a higher risk of infection.
PubMed: 38590588
DOI: 10.5455/msm.2024.36.90-96 -
Journal of Nephrology Sep 2023Peritoneal dialysis- (PD) related infections continue to be a major cause of morbidity and mortality in patients on renal replacement therapy via PD. However, despite... (Review)
Review
Peritoneal dialysis- (PD) related infections continue to be a major cause of morbidity and mortality in patients on renal replacement therapy via PD. However, despite the great efforts in the prevention of PD-related infectious episodes, approximately one third of technical failures are still caused by peritonitis. Recent studies support the theory that ascribes to exit-site and tunnel infections a direct role in causing peritonitis. Hence, prompt exit site infection/tunnel infection diagnosis would allow the timely start of the most appropriate treatment, thereby decreasing the potential complications and enhancing technique survival. Ultrasound examination is a simple, rapid, non-invasive and widely available procedure for tunnel evaluation in PD catheter-related infections. In case of an exit site infection, ultrasound examination has greater sensitivity in diagnosing simultaneous tunnel infection compared to the physical exam alone. This allows distinguishing the exit site infection, which will likely respond to antibiotic therapy, from infections that are likely to be refractory to medical therapy. In case of a tunnel infection, the ultrasound allows localizing the catheter portion involved in the infectious process, thus providing significant prognostic information. In addition, ultrasound performed after two weeks of antibiotic administration allows monitoring patient response to therapy. However, there is no evidence of the usefulness of ultrasound examination as a screening tool for the early diagnosis of tunnel infections in asymptomatic PD patients.
Topics: Humans; Catheter-Related Infections; Catheters, Indwelling; Peritoneal Dialysis; Anti-Bacterial Agents; Peritonitis
PubMed: 36939999
DOI: 10.1007/s40620-023-01589-w -
BioRxiv : the Preprint Server For... Dec 2023Gastric cancer is the fifth most diagnosed cancer in the world. Infection by the bacteria (HP) is associated with approximately 75% of gastric cancer cases. HP...
BACKGROUND
Gastric cancer is the fifth most diagnosed cancer in the world. Infection by the bacteria (HP) is associated with approximately 75% of gastric cancer cases. HP infection induces chronic gastric inflammation, damaging the stomach and fostering carcinogenesis. Most mechanistic studies on induced gastric cancer initiation are performed in mice and utilize either mouse-adapted strains of HP or the natural mouse pathogen (HF). Each of these infection models is associated with strengths and weaknesses. Here, we identified the differences in immunogenicity and gastric pathological changes associated with HP and HF infection in mice.
MATERIAL AND METHODS
PMSS1 HP strain or with the CS1 HF strain were co-cultured with mouse peritoneal macrophages to assess their immunostimulatory effects. C57BL/6J mice were infected with HP or HF, and gastric inflammation, atrophy, and metaplasia development were assessed 2 months post-infection.
RESULTS
HP and HF induced similar cytokine production from cultured mouse peritoneal macrophages. HP-infected mice caused modest inflammation within both the gastric corpus and antrum and did not induce significant atrophy within the gastric corpus. In contrast, HF induced significant inflammation throughout the gastric corpus and antrum. Moreover, HF infection was associated with significant atrophy of the chief and parietal cell compartments and induced expression of pyloric metaplasia markers.
CONCLUSIONS
HP is poorly immunogenic compared to HF. HF induces dramatic CD4+ T cell activation, which is associated with increased gastric cancer risk in humans. Thus, HP studies in mice are better suited for studies on colonization, while HF is more strongly suited for pathogenesis and cancer initiation studies.
PubMed: 38187587
DOI: 10.1101/2023.12.22.573128