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Cells Jun 2024Post-surgical abdominal adhesions, although poorly understood, are highly prevalent. The molecular processes underlying their formation remain elusive. This review aims... (Review)
Review
Post-surgical abdominal adhesions, although poorly understood, are highly prevalent. The molecular processes underlying their formation remain elusive. This review aims to assess the relationship between neutrophil extracellular traps (NETs) and the generation of postoperative peritoneal adhesions and to discuss methods for mitigating peritoneal adhesions. A keyword or medical subject heading (MeSH) search for all original articles and reviews was performed in PubMed and Google Scholar. It included studies assessing peritoneal adhesion reformation after abdominal surgery from 2003 to 2023. After assessing for eligibility, the selected articles were evaluated using the Critical Appraisal Skills Programme checklist for qualitative research. The search yielded 127 full-text articles for assessment of eligibility, of which 7 studies met our criteria and were subjected to a detailed quality review using the Critical Appraisal Skills Programme (CASP) checklist. The selected studies offer a comprehensive analysis of adhesion pathogenesis with a special focus on the role of neutrophil extracellular traps (NETs) in the development of peritoneal adhesions. Current interventional strategies are examined, including the use of mechanical barriers, advances in regenerative medicine, and targeted molecular therapies. In particular, this review emphasizes the potential of NET-targeted interventions as promising strategies to mitigate postoperative adhesion development. Evidence suggests that in addition to their role in innate defense against infections and autoimmune diseases, NETs also play a crucial role in the formation of peritoneal adhesions after surgery. Therefore, therapeutic strategies that target NETs are emerging as significant considerations for researchers. Continued research is vital to fully elucidate the relationship between NETs and post-surgical adhesion formation to develop effective treatments.
Topics: Extracellular Traps; Humans; Tissue Adhesions; Neutrophils; Postoperative Complications; Animals; Abdomen
PubMed: 38891123
DOI: 10.3390/cells13110991 -
Cells May 2024Acute inflammation is a rapid and dynamic process involving the recruitment and activation of multiple cell types in a coordinated and precise manner. Here, we...
Ly6C Monocytes Are Metabolically Reprogrammed in the Blood during Inflammatory Stimulation and Require Intact OxPhos for Chemotaxis and Monocyte to Macrophage Differentiation.
Acute inflammation is a rapid and dynamic process involving the recruitment and activation of multiple cell types in a coordinated and precise manner. Here, we investigate the origin and transcriptional reprogramming of monocytes using a model of acute inflammation, zymosan-induced peritonitis. Monocyte trafficking and adoptive transfer experiments confirmed that monocytes undergo rapid phenotypic change as they exit the blood and give rise to monocyte-derived macrophages that persist during the resolution of inflammation. Single-cell transcriptomics revealed significant heterogeneity within the surface marker-defined CD11bLy6GLy6C monocyte populations within the blood and at the site of inflammation. We show that two major transcriptional reprogramming events occur during the initial six hours of Ly6C monocyte mobilisation, one in the blood priming monocytes for migration and a second at the site of inflammation. Pathway analysis revealed an important role for oxidative phosphorylation (OxPhos) during both these reprogramming events. Experimentally, we demonstrate that OxPhos via the intact mitochondrial electron transport chain is essential for murine and human monocyte chemotaxis. Moreover, OxPhos is needed for monocyte-to-macrophage differentiation and macrophage M(IL-4) polarisation. These new findings from transcriptional profiling open up the possibility that shifting monocyte metabolic capacity towards OxPhos could facilitate enhanced macrophage M2-like polarisation to aid inflammation resolution and tissue repair.
Topics: Monocytes; Animals; Oxidative Phosphorylation; Macrophages; Cell Differentiation; Inflammation; Humans; Mice; Antigens, Ly; Chemotaxis; Mice, Inbred C57BL; Peritonitis; Zymosan; Mitochondria; Cellular Reprogramming
PubMed: 38891050
DOI: 10.3390/cells13110916 -
Cureus Jun 2024Immunotherapy has been shown to provide clinical benefit in selected patients with head and neck squamous cell carcinoma (HNSCC), regardless of human papillomavirus...
Immunotherapy has been shown to provide clinical benefit in selected patients with head and neck squamous cell carcinoma (HNSCC), regardless of human papillomavirus (HPV) infection, and including recurrent/metastatic (R/M) platinum refractory tumors. Hyperprogression is an uncommon negative outcome of treatment with immunotherapy. We present the case of a patient with HPV+ HNSCC who presented hyperprogression after immunotherapy and a rare metastasis location with peritoneal carcinomatosis and subcutaneous nodules. HPV+ HNSCC is related to distant recurrence after a longer interval of time and more diverse metastasis sites compared with HPV- disease. However, the literature on peritoneal metastasis in HNSCC remains limited, with few documented cases. To the best of our knowledge, this is the first case reporting peritoneal carcinomatosis after hyperprogression in HNSCC.
PubMed: 38887752
DOI: 10.7759/cureus.62509 -
Aging Jun 2024Microbial infection-induced sepsis causes excessive inflammatory response and multiple organ failure. An effective strategy for the treatment of sepsis-related syndromes...
Microbial infection-induced sepsis causes excessive inflammatory response and multiple organ failure. An effective strategy for the treatment of sepsis-related syndromes is still needed. Rosuvastatin, a typical β-hydroxy β-methylglutaryl-CoA reductase inhibitor licensed for reducing the levels of low-density lipoprotein cholesterol in patients with hyperlipidemia, has displayed anti-inflammatory capacity in different types of organs and tissues. However, its effects on the development of sepsis are less reported. Here, we found that the administration of Rosuvastatin reduced the mortality of sepsis mice and prevented body temperature loss. Additionally, it inhibited the production of inflammatory cytokines such as tumor necrosis factor (TNF-α), Interleukin-6 (IL-6), interleukin-1β (IL-1β), and migration inhibitory factor (MIF) in peritoneal lavage supernatants of animals. The increased number of mononuclear cells in the peritoneum of sepsis mice was reduced by Rosuvastatin. Interestingly, it ameliorated lung inflammation and improved the hepatic and renal function in the sepsis animals. Further experiments show that Rosuvastatin inhibited lipopolysaccharide (LPS)-induced production of proinflammatory cytokines in RAW 264.7 macrophages by preventing the activation of nuclear factor kappa-B (NF-κB). Our findings demonstrate that the administration of Rosuvastatin hampered organ dysfunction and mitigated inflammation in a relevant model of sepsis.
PubMed: 38885061
DOI: 10.18632/aging.205937 -
The Israel Medical Association Journal... Jun 2024Pseudomonas aeruginosa (PSA) is an infectious pathogen associated with acute appendicitis; however, it is not consistently addressed by empirical antibiotic therapy,...
BACKGROUND
Pseudomonas aeruginosa (PSA) is an infectious pathogen associated with acute appendicitis; however, it is not consistently addressed by empirical antibiotic therapy, despite potential complications.
OBJECTIVES
To investigate the incidence, predictors, and outcomes of PSA-associated acute appendicitis in children.
METHODS
We conducted a retrospective analysis involving pediatric patients who underwent acute appendicitis surgery and had positive peritoneal cultures. Clinical, microbiological, and intraoperative data were extracted from medical records.
RESULTS
Among 2523 children with acute appendicitis, 798 (31.6%) underwent peritoneal cultures, revealing 338 positive cases (42.3%), with PSA detected in 77 cases (22.8%). Children with PSA were three times more likely to exhibit high intraoperative grading ≥ 3 (93.4% vs. 76.8%, 95% confidence interval [95%CI] 1.2-8.3, P = 0.023) and nearly four times more likely to have polymicrobial cultures (88.3% vs. 62.1%, 95%CI 1.8-8.0, P < 0.001) than those without PSA in peritoneal cultures. Duration of symptoms did not predict PSA isolation (P = 0.827). Patients with PSA had longer median hospital stays (8 days, interquartile range [IQR] 7-10) than those with other pathogens (7 days, IQR 5-9) (P = 0.004). Antibiotic treatment duration, intensive care unit admission rates, readmission, and mortality were similar between the two groups (P = 0.893, 0.197, 0.760, and 0.761, respectively).
CONCLUSIONS
PSA is a common pathogen in children diagnosed with acute appendicitis and positive peritoneal cultures. The likelihood of isolating PSA increases with high-grade intraoperative assessment and in the presence of multiple pathogens in peritoneal cultures, suggests antipseudomonal treatment.
Topics: Humans; Appendicitis; Female; Pseudomonas aeruginosa; Child; Retrospective Studies; Male; Pseudomonas Infections; Incidence; Anti-Bacterial Agents; Length of Stay; Appendectomy; Acute Disease; Israel; Adolescent; Child, Preschool
PubMed: 38884308
DOI: No ID Found -
Medical Mycology Case Reports Jun 2024We present the first case report of peritoneal dialysis (PD)-associated peritonitis due to , with the same pathogen detected in her caregiver's tinea capitis. This...
We present the first case report of peritoneal dialysis (PD)-associated peritonitis due to , with the same pathogen detected in her caregiver's tinea capitis. This confirms that touch contamination from the caregiver's infection was the primary source of this rare organism. The species of pathogen causing peritonitis and her caregiver's scalp lesions were identified by DNA barcoding. The patient responded well to timely PD catheter removal and a 2-week course of systemic amphotericin B deoxycholate. Preventive strategies should prioritize hygiene practices, including maintaining adequate personal hygiene and practicing thorough hand washing, to mitigate the risk of touch contamination and subsequent infection with fungal pathogens.
PubMed: 38884003
DOI: 10.1016/j.mmcr.2024.100653 -
JHEP Reports : Innovation in Hepatology Jun 2024Patients with advanced cirrhosis often develop hepatic decompensation, which is accompanied by systemic inflammation and may eventually lead to acute-on-chronic liver...
BACKGROUND & AIMS
Patients with advanced cirrhosis often develop hepatic decompensation, which is accompanied by systemic inflammation and may eventually lead to acute-on-chronic liver failure. One important cause of systemic hyperinflammation is a dysregulated overshooting immune response in ascites in the abdominal cavity. In this study, we analyzed the role of CD8 T cells in the ascites immune compartment.
METHODS
Peripheral blood and ascites fluid were collected from 50 patients with decompensated cirrhosis. Phenotype and functional responses of CD8 T cells were analyzed, and obtained data were compared with each other as well as with healthy controls and patients with compensated cirrhosis.
RESULTS
High-dimensional flow cytometry revealed that CD8 T cells are abundant in the ascites of patients with cirrhosis and exhibit a chronically activated bystander phenotype with innate-like functions. Indeed, we identified distinct CXCR6CD69 clusters of late effector memory CD8 T cells that were rarely found in blood and correlated with clinical parameters of disease severity. Moreover, this CD8 T-cell population was hyperresponsive to innate cytokines and exhibited cytokine-mediated bystander activation. Interestingly, the Janus kinase (JAK) inhibitor tofacitinib was able to effectively block bystander-activated CXCR6CD69 CD8 T cells and significantly suppress effector molecule production.
CONCLUSIONS
The results indicate that CXCR6CD69 CD8 T cells in ascites are associated with disease severity and may contribute to inflammation in patients with decompensated cirrhosis, suggesting that targeted inhibition of this immune cell subset may be a viable therapeutic option.
IMPACT AND IMPLICATIONS
Patients with advanced cirrhosis often develop hepatic decompensation, which is accompanied by systemic inflammation and eventually leads to acute-on-chronic liver failure. One important cause of systemic hyperinflammation is a dysregulated overshooting immune response in ascites in the abdominal cavity. In this study, we demonstrate that CXCR6CD69 CD8 T cells are abundant in the ascites of patients with cirrhosis, exhibit a chronically activated bystander phenotype, and correlate with clinical parameters of disease severity. Moreover, we show that the Janus kinase (JAK) inhibitor tofacitinib can effectively block these bystander-activated CXCR6CD69 CD8 T cells, suggesting that targeted inhibition of this immune cell subset may be a potential therapeutic strategy.
CLINICAL TRIAL NUMBER
Prospective registry: INFEKTA (DRKS00010664).
PubMed: 38882602
DOI: 10.1016/j.jhepr.2024.101074 -
Medicine Jun 2024Urachal anomalies are rare and can present with various clinical manifestations. Urachal remnants, in particular, can be difficult to diagnose because of atypical...
RATIONALE
Urachal anomalies are rare and can present with various clinical manifestations. Urachal remnants, in particular, can be difficult to diagnose because of atypical symptoms at presentation. This study reports a case of intestinal obstruction in an infant secondary to an infected urachal cyst.
PATIENTS CONCERNS
A 3-month-old boy with a known febrile urinary tract infection developed acute abdominal distension.
DIAGNOSES
Abdominal ultrasound (US) and computed tomography (CT) revealed a nonspecific, ill-defined soft tissue density at the mid-abdomen, associated with intestinal obstruction.
INTERVENTIONS
Emergency exploratory laparotomy was performed. The site of the obstruction was found to be at the mid-small bowel; the proximal small bowel was markedly distended, and the small bowel and sigmoid colon were adherent to urachal remnant. The urachal remnant was excised, and the peritoneal adhesions were lysed.
OUTCOMES
The day after surgery, the patient was discharged without any complications.
LESSONS
Intestinal obstruction is an exceedingly rare presentation of urachal remnants. This case highlights that urachal anomalies should be considered in the differential diagnosis in patients with intestinal obstruction and a concurrent febrile urinary tract infection.
Topics: Humans; Male; Urinary Tract Infections; Urachal Cyst; Infant; Intestinal Obstruction; Fever; Diagnosis, Differential; Ultrasonography
PubMed: 38875366
DOI: 10.1097/MD.0000000000038615 -
Frontiers in Cellular and Infection... 2024Serratia marcescens, as a Gram-negative opportunistic pathogen, is a rare cause of peritonitis and has worse clinical outcomes than Gram-positive peritonitis. In this... (Review)
Review
Serratia marcescens, as a Gram-negative opportunistic pathogen, is a rare cause of peritonitis and has worse clinical outcomes than Gram-positive peritonitis. In this case report, we describe a case of Serratia marcescens associated peritonitis that was successfully cured without catheter removal. A 40-year-old male patient with peritoneal dialysis who worked in the catering industry was admitted to the hospital for 16 hours after the discovery of cloudy peritoneal dialysate and abdominal pain. Ceftazidime and cefazolin sodium were immediately given intravenously as an empirical antibiotic regimen. After detecting Serratia marcescens in the peritoneal diasate culture, the treatment was switched to ceftazidime and levofloxacin. The routine examination of peritoneal dialysate showed a significant decrease in white blood cells, the peritoneal dialysate became clear, and the peritoneal dialysis catheter was retained. The patient was treated for 2 weeks and treated with oral antibiotics for 1 week. It is necessary to further strengthen the hygiene of work environment to prevent Serratia marcescens infection in peritoneal dialysis patients. We recommend that patients with Serratia marcescens associated peritonitis should be treated with a combination of antibiotics as early as possible empirically, and at the same time, the peritoneal dialysis fluid culture should be improved, and the antibiotic regimen should be timely adjusted according to the drug sensitivity results. For patients with clinical symptoms for more than 3 days, considering the strong virulence of Serratia marcescens, whether to use meropenem directly or not can provide a reference for clinical decision-making. Further clinical studies are needed to achieve more precise anti-infective treatment.
Topics: Humans; Serratia marcescens; Male; Peritonitis; Adult; Serratia Infections; Anti-Bacterial Agents; Peritoneal Dialysis; Treatment Outcome; Device Removal; Levofloxacin; Ceftazidime; Cefazolin
PubMed: 38873095
DOI: 10.3389/fcimb.2024.1373036 -
Virology Journal Jun 2024Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four...
BACKGROUND
Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four years after the start of the COVID-19 pandemic, crucial knowledge on the immune responses in these patient groups is still lacking. Therefore, this study aimed at investigating the humoral immune response after a SARS-CoV-2 infection compared to vaccination as well as the evolution of immunoglobulins over time.
METHODS
Kidney transplant recipients, patients on haemodialysis or on peritoneal dialysis and healthy controls were included in this longitudinal multicenter study. SARS-CoV-2 anti-RBD, anti-NP and anti-S1S2 immunoglobulin G (IgG) and A (IgA) as well as the neutralizing antibody capacity were measured.
RESULTS
Kidney transplant recipients had a significantly better humoral response to SARS-CoV-2 after infection (86.4%) than after a two-dose mRNA vaccination (55.8%) while seroconversion was comparable in patients on haemodialysis after infection (95.8%) versus vaccination (89.4%). In individuals without prior COVID-19, the IgG levels after vaccination were significantly lower in kidney transplant recipients when compared to all other groups. However, the IgA titres remained the highest in this patient group at each time point, both after infection and vaccination. A history COVID-19 was associated with higher antibody levels after double-dose vaccination in all patient categories and, while decreasing, titres remained high six months after double-dose vaccination.
CONCLUSION
Kidney transplant recipients had a more robust humoral response to SARS-CoV-2 following infection compared to a two-dose mRNA vaccination, while patients on haemodialysis exhibited comparable seroconversion rates. Notably, individuals with prior COVID-19 exhibited higher IgG levels in response to vaccination. Hybrid immunity is thus the best possible defence against severe COVID-19 disease and seems also to hold up for these populations. Next, it is not clear whether the higher IgA levels in the kidney transplant recipients is beneficial for neutralizing SARS-CoV-2 or if it is a sign of disease severity.
Topics: Humans; Kidney Transplantation; COVID-19; Immunoglobulin G; Male; Female; Immunoglobulin A; Middle Aged; Antibodies, Viral; SARS-CoV-2; Immunity, Humoral; Renal Dialysis; Transplant Recipients; Antibodies, Neutralizing; Vaccination; Aged; Adult; Longitudinal Studies; COVID-19 Vaccines; Spike Glycoprotein, Coronavirus
PubMed: 38872127
DOI: 10.1186/s12985-024-02410-1