-
Proceedings of the National Academy of... Jul 2024The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase...
The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine biosynthesis, has been well documented in lymphocytes, its role in the myeloid compartment is less understood. Here, we identify a significant population of macrophages (Mϕs) expressing ChAT and synthesizing acetylcholine in the resolution phase of acute peritonitis. Using -GFP reporter mice, we observed marked upregulation of ChAT in monocyte-derived small peritoneal Mϕs (SmPMs) in response to Toll-like receptor agonists and bacterial infections. These SmPMs, phenotypically and transcriptionally distinct from tissue-resident large peritoneal macrophages, up-regulated ChAT expression through a MyD88-dependent pathway involving MAPK signaling. Notably, this process was attenuated by the TRIF-dependent TLR signaling pathway, and our tests with a range of neurotransmitters and cytokines failed to induce a similar response. Functionally, deficiency in Mϕs led to significantly decreased peritoneal acetylcholine levels, reduced efferocytosis of apoptotic neutrophils, and a delayed resolution of peritonitis, which were reversible with exogenous ACh supplementation. Intriguingly, despite B lymphocytes being a notable ChAT-expressing population within the peritoneal cavity, deletion in B cells did not significantly alter the resolution process. Collectively, these findings underscore the crucial role of Mϕ-derived acetylcholine in the resolution of inflammation and highlight the importance of the non-neuronal cholinergic system in immune regulation.
Topics: Animals; Choline O-Acetyltransferase; Peritonitis; Mice; Macrophages, Peritoneal; Acetylcholine; Myeloid Differentiation Factor 88; Mice, Inbred C57BL; Signal Transduction; Inflammation; B-Lymphocytes; Toll-Like Receptors; Phagocytosis; Macrophages; Mice, Knockout
PubMed: 38923993
DOI: 10.1073/pnas.2402143121 -
Tomography (Ann Arbor, Mich.) Jun 2024Cystic echinococcosis is a zoonotic parasitic disease that affects the liver in more than 70% of cases, and there is still an underestimated incidence in endemic areas.... (Review)
Review
Cystic echinococcosis is a zoonotic parasitic disease that affects the liver in more than 70% of cases, and there is still an underestimated incidence in endemic areas. With a peculiar clinical presentation that ranges from paucisymptomatic illness to severe and possibly fatal complications, quality imaging and serological studies are required for diagnosis. The mainstay of treatment to date is surgery combined with antiparasitic agents. The surgical armamentarium consists of open and laparoscopic procedures for selected cases with growing confidence in parenchyma-sparing interventions. Endoscopic retrograde cholangiopancreatography (ERCP) is extremely useful for the diagnosis and treatment of biliary fistulas. Recent relevant studies in the literature are reviewed, and two complex cases are presented. The first patient underwent open surgery to treat 11 liver cysts, and during the follow-up, a right pulmonary cyst was diagnosed that was treated by minimally invasive surgery. The second case is represented by the peritoneal rupture of a giant liver cyst in a young woman who underwent laparoscopic surgery. Both patients developed biliary fistulas that were managed by ERCP. Both patients exhibited a non-specific clinical presentation and underwent several surgical procedures combined with antiparasitic agents, highlighting the necessity of customized treatment in order to decrease complications and successfully cure the disease.
Topics: Female; Humans; Biliary Fistula; Cholangiopancreatography, Endoscopic Retrograde; Echinococcosis, Hepatic; Laparoscopy; Liver; Tomography, X-Ray Computed
PubMed: 38921947
DOI: 10.3390/tomography10060070 -
Pathogens (Basel, Switzerland) May 2024Coronavirus frequently infects humans and animals, showing the ability to recombine and cross over to different species. Cats can be considered a model for studying...
Coronavirus frequently infects humans and animals, showing the ability to recombine and cross over to different species. Cats can be considered a model for studying coronavirus infection, in which feline coronavirus (FCoV) represents a major enteric pathogen related to gastroenteric disease. In this animal, the virus can acquire tropism for macrophage cells, leading to a deadly disease called feline infectious peritonitis (FIP). In this study, monocyte-derived macrophages were isolated by CD14-positive selection in venous whole blood from 26 cats with FIP and 32 FCoV-positive healthy cats. Phagocytosis and respiratory burst activities were investigated and compared between the groups. This is the first study comparing macrophage activity in cats affected by FIP and healthy cats positive for FCoV infection. Our results showed that in cats with FIP, the phagocytic and respiratory burst activities were significantly lower. Our results support the possible role of host immunity in Coronaviridae pathogenesis in cats, supporting future research on the immune defense against this systemic disease.
PubMed: 38921735
DOI: 10.3390/pathogens13060437 -
Journal of Leukocyte Biology Jun 2024Macrophages are essential immune cells for host defense against bacterial pathogens after radiation injury. However, the role of macrophage phagocytosis in infection...
Macrophages are essential immune cells for host defense against bacterial pathogens after radiation injury. However, the role of macrophage phagocytosis in infection following radiation injury remains poorly examined. Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern that dysregulates host immune system responses such as phagocytosis. We hypothesized that radiation-induced eCIRP release impairs macrophage phagocytosis of bacteria. Adult healthy mice were exposed to 6.5-Gy total body irradiation (TBI). Primary peritoneal macrophages isolated from adult healthy mice were exposed to 6.5-Gy radiation. eCIRP-neutralizing monoclonal antibody (mAb) was added to the cell culture prior to irradiation. Bacterial phagocytosis by peritoneal macrophages was assessed using pHrodo Green-labeled E. coli 7 days after irradiation ex vivo and in vitro. Bacterial phagocytosis was also assessed after treatment with recombinant murine CIRP (rmCIRP). Rac1 and ARP2 protein expression in cell lysates and eCIRP levels in the peritoneal lavage were assessed by Western blotting. Bacterial phagocytosis by peritoneal macrophages was significantly decreased after irradiation compared to controls ex vivo and in vitro. Rac1 and ARP2 expression in the peritoneal macrophages were downregulated after TBI. TBI significantly increased eCIRP levels in the peritoneal cavity. rmCIRP significantly decreased bacterial phagocytosis in a dose-dependent manner. eCIRP mAb restored bacterial phagocytosis by peritoneal macrophages after irradiation. Ionizing radiation exposure impairs bacterial phagocytosis by macrophages after irradiation. Neutralization of eCIRP restores the phagocytic ability of macrophages after irradiation. Our findings elucidate a novel mechanism of immune dysfunction and provide a potential new therapeutic approach for limiting infection after radiation injury.
PubMed: 38920274
DOI: 10.1093/jleuko/qiae132 -
Perioperative Medicine (London, England) Jun 2024Secondary peritonitis is the second leading cause of sepsis worldwide. Drug resistance to peritoneal cavity bacterial infection remains a public health threat,...
INTRODUCTION
Secondary peritonitis is the second leading cause of sepsis worldwide. Drug resistance to peritoneal cavity bacterial infection remains a public health threat, especially in resource-limited settings in Africa, including Uganda. This study aimed to determine the antibacterial susceptibility patterns and factors associated with secondary peritonitis among patients with acute abdomen who underwent surgery at a Regional Referral Hospital in Uganda.
METHODS
This was a cross-sectional study conducted at Hoima Regional Referral Hospital (HRRH) that enrolled 126 patients with acute abdomen. Clinical samples were aseptically collected at laparotomy from patients with secondary peritonitis for culture and sensitivity using standard Microbiological methods. Binary logistic regression was used to identify factors associated with secondary peritonitis among patients with acute abdomen.
RESULTS
The majority of the patients were males (61.9%) with a mean age of 37.9(SD ± 21.8). Secondary peritonitis was found in 57(45.2%) of the patients. Gram-negative bacteria were the most commonly isolated organisms with Escherichia coli (35.8%) and Klebsiella spp (17.0%) predominating. Imipenem 88.8%(8/9), Amikacin 88.8%(8/9), Ciprofloxacin 44.4%(4/9) and Gentamicin 44.4%(4/9) demonstrated sensitivity to the different isolated organisms at varying degrees. Being a male (AOR = 3.658; 95% CI = 1.570-8.519, p = 0.003) and presenting 3 days after onset of symptoms (AOR = 2.957; 95% CI = 1.232-7.099, p = 0.015) were independently associated with secondary peritonitis.
CONCLUSION
Imipenem, Amikacin, Ciprofloxacin, and Gentamicin should be considered for empirical therapy in cases of secondary peritonitis. Patients, more especially males with abdominal pain should be encouraged to present early to the hospital to minimize progression to secondary peritonitis.
PubMed: 38915124
DOI: 10.1186/s13741-024-00425-4 -
Clinical and Experimental Nephrology Jun 2024This review outlines the epidemiology, characteristics, risk factors, and prognosis of peritoneal dialysis (PD)-related peritonitis, PD catheter-related infections, and... (Review)
Review
This review outlines the epidemiology, characteristics, risk factors, and prognosis of peritoneal dialysis (PD)-related peritonitis, PD catheter-related infections, and the effects of assisted PD in elderly patients from the Japanese perspective. Based on the literature, the incidence of peritonitis is likely to be higher in elderly patients than in younger patients. The most frequent causative bacteria in elderly patients are Gram-positive bacteria, as in adult PD patients, most commonly due to transcatheter infection. However, elderly patients may have difficulty recognizing cloudy drainage fluid due to decreased visual acuity. Hypokalemia, the use of gastric acid suppressants, prophylactic antibiotic use before endoscopy, biocompatible fluids and hypoalbuminemia considered modifiable risk factors for peritonitis. However, the mechanism by which treatment of hypokalemia prevents peritonitis is unknown. Currently, the relationship between gastric acid suppression therapy and peritonitis in elderly patients is debatable, with no evidence to strongly recommend uniform discontinuation of gastric acid suppression therapy. Exit-site infection (ESI) is a major risk factor for the development of peritonitis, and appropriate prevention and management of ESI may reduce infection-related hospitalizations in PD patients. Currently, no randomized, controlled trials have verified the effectiveness of antibiotic application for ESI in Japan, but results from other countries are awaited. In assisted PD, it is extremely important that family members, caregivers, and nurses who support the procedure receive sufficient education and training from medical professionals familiar with PD. Early detection and treatment of PD-related infections are required because the risk of death increases in elderly patients.
PubMed: 38914913
DOI: 10.1007/s10157-024-02531-5 -
Clinical Kidney Journal Jun 2024
PubMed: 38912223
DOI: 10.1093/ckj/sfae136 -
Infection and Drug Resistance 2024In this study we aimed to evaluate the postoperative safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the...
Postoperative Bloodstream Infections in Patients with Peritoneal Surface Malignancies Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Risk Factors and Pathogen Resistance.
OBJECTIVE
In this study we aimed to evaluate the postoperative safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies (PSM), and analyzed the risk factors and pathogen resistance associated with bloodstream infections.
METHODS
We retrospectively analyzed the incidence of postoperative bloodstream infections in 1500 patients undergoing CRS and HIPEC for PSM. We utilized univariate and multivariate analyses to screen for independent risk factors associated with postoperative bloodstream infections in CRS combined with HIPEC.
RESULTS
Among the 1500 cases of individuals undergoing CRS combined with HIPEC, 207 cases (13.8%) experienced bloodstream infections. A total of 233 strains of pathogens were isolated and cultured, consisting of 151 gram-positive cocci, 52 gram-negative bacilli, and 30 fungi. Coagulase-negative staphylococci (SCN) were the gram-positive cocci (54.94%), while (7.30%) and (5.58%) dominated the Gram-negative bacilli. was the predominant fungus. Staphylococci exhibited high sensitivity to tigecycline, linezolid, vancomycin, and quinupristin/dalfopristin. However, and were resistant to imipenem. Furthermore, five parameters were associated with the development of bloodstream infections: age ( = 0.040), surgical history ( = 0.033), prior tumor treatment ( < 0.001), tumor tissue type ( = 0.034), and completeness of cytoreduction (CC) score ( = 0.004). Among these, age ( = 0.013), prior tumor treatment ( = 0.001), tumor tissue type ( = 0.032), and CC score ( = 0.002) emerged as independent risk factors for postoperative bloodstream infections in patients undergoing CRS combined with HIPEC.
CONCLUSION
Postoperative bloodstream infections in patients with PSM undergoing CRS combined with HIPEC are predominantly attributed to SCN, , and . Notably, Enterobacteriaceae exhibited resistance to carbapenem. Independent risk factors for postoperative infections in PSM include age, prior tumor treatment, tumor tissue type, and completeness of cytoreduction score.
PubMed: 38912220
DOI: 10.2147/IDR.S462639 -
Gynecology and Minimally Invasive... 2024Vault closure is the final step to hysterectomy, protecting the abdominal cavity from the exterior environment. Thus, closure becomes crucial in preventing ascend of...
OBJECTIVES
Vault closure is the final step to hysterectomy, protecting the abdominal cavity from the exterior environment. Thus, closure becomes crucial in preventing ascend of infection to the peritoneal cavity. Our study aims to compare vault closure between laparoscopic and vaginal routes, their operating time, and postoperative complications.
MATERIALS AND METHODS
The ambispective comparative study was done in a tertiary care teaching center from June 2016 to December 2022. Three hundred and forty-four patients were included in the study that underwent a total laparoscopic hysterectomy. Interventions - Patients who had laparoscopic vault closure were in Group 1 ( = 198) and those who had vaginal closure were in Group 2 ( = 146). The results were compared. It included age, body mass index of the patient, the indication of surgery, intraoperative blood loss, size of the uterus, time taken during vault closure, and postoperative complications.
RESULTS
The time taken by laparoscopic vault repair was significantly less than vaginal repair (19.7 ± 13.3 min vs. 30.1 ± 6.6 min, < 0.001). There was postoperative vault infection (2.7%), vault hematoma (1.3%), and no vault prolapse seen in vaginal repair. The organisms isolated were mainly , , and .
CONCLUSION
Laparoscopic vault closure has shown significantly improved results compared to vaginal route repair.
PubMed: 38911314
DOI: 10.4103/gmit.gmit_8_23 -
Gynecology and Minimally Invasive... 2024We aimed to evaluate the surgical results for ectopic pregnancy (EP) treated at Fukushima Red Cross Hospital for over a 20-year period from 2002 to 2021.
OBJECTIVES
We aimed to evaluate the surgical results for ectopic pregnancy (EP) treated at Fukushima Red Cross Hospital for over a 20-year period from 2002 to 2021.
MATERIALS AND METHODS
We evaluated the incidence, surgical procedures, site of implantation, amount of hemoperitoneum, and the proportion of cases with risk factors of EP.
RESULTS
Two hundred and fifty-nine cases of EP were treated surgically. The incidence of EP seemed to be gradually decreasing in recent years. By pregnancy site, 235 (90.7%) of EPs were tubal pregnancies (TPs), 13 in interstitial pregnancies (IPs), 7 in ovarian pregnancies, and 4 in peritoneal pregnancies. For IPs, human chorionic gonadotropin (hCG) levels were statistically higher than with TP and intraperitoneal bleeding was less than with other EP sites. Thirty-nine patients (15.0%) were with massive hemoperitoneum (>500 mL), and laparoscopic surgery was performed in all patients with massive hemoperitoneum except in two patients. The proportion of cases with risk factors for EP such as infection or history of smoking was 5.4% and 40.6%, respectively. Epidemiological research shows that the number of patients with chlamydia infection, rates of smokers, or the occurrence of EP with assisted reproductive technology has been decreasing in recent years in Japan.
CONCLUSION
Appropriate surgical intervention should be selected while considering such as facility capabilities, context, and surgeon skill, especially in critical cases, such as cases involving massive hemoperitoneum and hemorrhagic shock. The recent presumed decrease in the occurrence of EP may partly be associated with the decrease in the occurrence of risk factors.
PubMed: 38911310
DOI: 10.4103/gmit.gmit_53_23