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Frontiers in Immunology 2024Fibroblastic reticular cells (FRCs) are a subpopulation of stromal cells modulating the immune environments in health and disease. We have previously shown that...
Fibroblastic reticular cells (FRCs) are a subpopulation of stromal cells modulating the immune environments in health and disease. We have previously shown that activation of TLR9 signaling in FRC in fat-associated lymphoid clusters (FALC) regulate peritoneal immunity via suppressing immune cell recruitment and peritoneal resident macrophage (PRM) retention. However, FRCs are heterogeneous across tissues and organs. The functions of each FRC subset and the regulation of TLR9 in distinct FRC subsets are unknown. Here, we confirmed that specific deletion of TLR9 in FRC improved bacterial clearance and survival during peritoneal infection. Furthermore, using single-cell RNA sequencing, we found two subsets of FRCs (CD55 and CD55) in the mesenteric FALC. The CD55 FRCs were enriched in gene expression related to extracellular matrix formation. The CD55 FRCs were enriched in gene expression related to immune response. Interestingly, we found that TLR9 is dominantly expressed in the CD55 subset. Activation of TLR9 signaling suppressed proliferation, cytokine production, and retinoid metabolism in the CD55 FRC, but not CD55 FRC. Notably, we found that adoptive transfer of CD55 FRC from mesenteric FALC more effectively improved the survival during peritonitis compared with WT-FRC or CD55 FRC. Furthermore, we identified CD55 and CD55 subsets in human adipose tissue-derived FRC and confirmed the suppressive effect of TLR9 on the proliferation and cytokine production in the CD55 subset. Therefore, inhibition of TLR9 in the CD55 FRCs from adipose tissue could be a useful strategy to improve the therapeutic efficacy of FRC-based therapy for peritonitis.
Topics: Animals; Toll-Like Receptor 9; Mice; Peritonitis; Signal Transduction; Fibroblasts; Mice, Knockout; Mice, Inbred C57BL; Immunomodulation; Male; Humans; Disease Models, Animal
PubMed: 38827745
DOI: 10.3389/fimmu.2024.1337384 -
Journal of Pharmaceutical and... Sep 2024GS-441524 is an adenosine nucleoside antiviral demonstrating significant efficacy in the treatment of feline infectious peritonitis (FIP), an otherwise fatal illness,...
GS-441524 is an adenosine nucleoside antiviral demonstrating significant efficacy in the treatment of feline infectious peritonitis (FIP), an otherwise fatal illness, resulting from infection with feline coronavirus. However, following the emergence of COVID-19, veterinary development was halted, and Gilead pursued clinical development of a GS-441524 pro-drug, resulting in the approval of Remdesivir under an FDA emergency use authorization. Despite lack of regulatory approval, GS-441524 is available without a prescription through various unlicensed online distributors and is commonly purchased by pet owners for the treatment of FIP. Herein, we report data obtained from the analytical characterization of two feline renal calculi, demonstrating the propensity for GS-441524 to cause renal toxicity through drug-induced crystal nephropathy in vivo. As definitive diagnosis of drug-induced crystal nephropathy requires confirmation of the lithogenic material to accurately attribute a mechanism of toxicity, renal stone composition and crystalline matrix were characterized using ultra-performance liquid chromatography photodiode array detection (UPLC-PDA), ultra-performance liquid chromatography mass spectrometry (LCMS), nuclear magnetic resonance (NMR) spectroscopy, X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). This work serves to provide the first analytical confirmation of GS-441524-induced crystal nephropathy in an effort to support toxicologic identification of adverse renal effects caused by administration of GS-441524 or any pro-drug thereof.
Topics: Animals; Adenosine Monophosphate; Alanine; Antiviral Agents; Cats; Kidney Calculi; COVID-19 Drug Treatment; Adenosine; Cat Diseases; Chromatography, High Pressure Liquid; Magnetic Resonance Spectroscopy
PubMed: 38823223
DOI: 10.1016/j.jpba.2024.116248 -
Cureus Apr 2024Peritonitis is a critical complication in peritoneal dialysis, often leading to peritoneal dialysis (PD) treatment failure. We present a rare case of (NS)-related...
Peritonitis is a critical complication in peritoneal dialysis, often leading to peritoneal dialysis (PD) treatment failure. We present a rare case of (NS)-related peritonitis in a 47-year-old male with multiple comorbidities. Despite NS's infrequent association with infections, prompt diagnosis and antibiotic therapy based on International Society for Peritoneal Dialysis (ISPD) guidelines led to a favorable outcome. This case emphasizes identifying uncommon pathogens in immunocompromised individuals and highlights the importance of prompt treatment to prevent morbidity.
PubMed: 38817497
DOI: 10.7759/cureus.59358 -
The Journal of Biological Chemistry May 2024Infiltration of monocyte-derived cells to sites of infection and injury is greater in males than in females, due in part, to increased chemotaxis, the process of...
Infiltration of monocyte-derived cells to sites of infection and injury is greater in males than in females, due in part, to increased chemotaxis, the process of directed cell movement toward a chemical signal. The mechanisms governing sexual dimorphism in chemotaxis are not known. We hypothesized a role for the store-operated calcium entry (SOCE) pathway in regulating chemotaxis by modulating leading and trailing edge membrane dynamics. We measured the chemotactic response of bone marrow-derived macrophages migrating toward complement component 5a (C5a). Chemotactic ability was dependent on sex and inflammatory phenotype (M0, M1, and M2), and correlated with SOCE. Notably, females exhibited a significantly lower magnitude of SOCE than males. When we knocked out the SOCE gene, stromal interaction molecule 1 (STIM1), it eliminated SOCE and equalized chemotaxis across both sexes. Analysis of membrane dynamics at the leading and trailing edges showed that STIM1 influences chemotaxis by facilitating retraction of the trailing edge. Using BTP2 to pharmacologically inhibit SOCE mirrored the effects of STIM1 knockout, demonstrating a central role of STIM/Orai-mediated calcium signaling. Importantly, by monitoring the recruitment of adoptively transferred monocytes in an in vivo model of peritonitis, we show that increased infiltration of male monocytes during infection is dependent on STIM1. These data support a model in which STIM1-dependent SOCE is necessary and sufficient for mediating the sex difference in monocyte recruitment and macrophage chemotactic ability by regulating trailing edge dynamics.
PubMed: 38815866
DOI: 10.1016/j.jbc.2024.107422 -
Heliyon May 2024No markers have been used to diagnose historical peritoneal dialysis (PD)-related peritonitis. Cyclophilin A (CypA) is associated with glucose toxicity and inflammation....
INTRODUCTION
No markers have been used to diagnose historical peritoneal dialysis (PD)-related peritonitis. Cyclophilin A (CypA) is associated with glucose toxicity and inflammation. We hypothesize that dialysate CypA can be a marker for historical peritonitis (at least 3 months free from peritonitis).
METHOD
An enzyme-linked immunosorbent assay kit was used to measure the concentration of dialysate CypA. Clinical and laboratory data were collected to correlate with historical peritonitis. Mann-Whitney test and -square test were used for analysis. Receiver operating characteristic (ROC) analysis was used to evaluate predictive power.
RESULTS
Out of a total of 31 patients who had undergone PD for at least 2 years, 18 had no history of PD-related peritonitis, while 13 had experienced PD-related peritonitis at least once. Overall, the patients in this population were in good health (normal white blood cell count, no anemia, normal electrolyte and serum albumin levels). There were no significant differences between patients with and without a history of peritonitis, except for blood white blood cell count (5650.6 ± 1848.4 vs. 7154.6 ± 2056.8, p = 0.032) and dialysate CypA value (24.27 ± 22.715 vs. 54.41 ± 45.63, p = 0.020). In the univariate analysis, only the dialysate CypA level showed a statistically significant association with historical peritonitis (HR = 1.030, 95 % CI = 1.010-1.062, p = 0.046). The AUC for dialysate CypA (>34.83 ng/mL) was 0.748, with a sensitivity of 0.615 and specificity of 0.833.
CONCLUSION
PD peritonitis poses a significant threat to the long-term use of peritoneal dialysis. Based on our study, even in the absence of concurrent infection, dialysate CypA can serve as a predictive marker for historical peritonitis, demonstrating high predictive power along with fair sensitivity and good specificity.
PubMed: 38813216
DOI: 10.1016/j.heliyon.2024.e31021 -
Therapeutic Advances in Gastroenterology 2024Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE);...
INTRODUCTION
Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE); however, it has been suggested that it may play a crucial role in reducing infections in these populations.
AIM
To evaluate the role of rifaximin in preventing frequent cirrhosis-related infections [spontaneous bacterial peritonitis, pneumonia, urinary tract infection (UTI), and bacteremia], e infection, and all-cause mortality, as well as determining adverse effects and adherence to the drug.
METHODS
A retrospective cohort study was conducted on decompensated cirrhotic patients with history of HE between January 2017 and November 2022 at a university center. Patients with cirrhosis, regardless of their etiology and severity, were included in the study, encompassing both hospitalized and outpatient cases. The statistical analysis included adjusted general linear models, Poisson regressions, and propensity score matching.
RESULTS
We included 153 patients. The mean age in the cohort was 60.2 ± 12.3 years and 67 (43.8%) were women. The main cause of cirrhosis was metabolic dysfunction-associated steatotic liver disease 52 (38%), and the median Model of End-Stage Liver Disease sodium was 16.5 (7-32). In the cohort, 65 (45%) patients used rifaximin. The mean follow-up was 32 months. Eighty-five patients with infectious events were recorded, and a total of 164 infectious events were registered. The main infectious events were UTIs (62, 37.8%) and pneumonia (38, 23.2%). The use of rifaximin was associated with lower infection rates, displaying an incidence rate ratio (IRR) of 0.64 [95% confidence interval (CI) (0.47-0.89); = 0.008]. However, no discernible impact on mortality outcome was observed [IRR 1.9, 95% CI (0.9-4.0); = 0.09]. There were no reported adverse effects, and no patient discontinued the therapy due to adverse effects.
CONCLUSION
The use of rifaximin significantly reduces infections in patients with cirrhosis and HE. Despite rifaximin was associated with a decreased all-cause mortality, this impact was not statistically significant in the adjusted analysis.
PubMed: 38812703
DOI: 10.1177/17562848241254267 -
Frontiers in Pediatrics 2024Acute appendicitis secondary to parasitic infections is uncommon, being detected in less than 1% of cases. Balantidium coli is a parasite found in pigs and primates with...
INTRODUCTION
Acute appendicitis secondary to parasitic infections is uncommon, being detected in less than 1% of cases. Balantidium coli is a parasite found in pigs and primates with zoonotic potential. To date, only three cases of acute appendicitis induced by this parasite have been documented globally.
CASE
A 7-year-old female patient, who consumed pork daily, presented to the emergency department with a one-day history of abdominal pain in the lower quadrants, described as colic-like, alongside abdominal distension. Initial abdominal radiography led to a diagnosis of intestinal obstruction. Conservative management without therapeutic response necessitated referral to a higher complexity center. Upon admission, an abdominal computed tomography scan diagnosed acute appendicitis and secondary ileus. During surgical intervention, an appendiceal phlegmon formed by loops of the small intestine was mechanically released, revealing a perforated appendix with extensive fecal peritoneal contamination. Pathological analysis identified an inflammatory infiltrate and the presence of Balantidium coli trophozoites. Medical treatment included Piperacillin-Tazobactam and Metronidazole. The patient was discharged after 10 days of medical treatment.
DISCUSSION
Acute appendicitis caused by Balantidium coli is a rare occurrence. It is crucial to identify parasites in pathological samples due to their impact on postoperative management. The close contact between humans and pigs, especially in developing countries, suggests that the prevalence of parasitic infection and colonization by Balantidium coli may be higher than currently recognized. Regarding the identification of this patient's specific exposure, the regular consumption of pork suggests the hypothesis that improper processing is linked to the acquisition of the parasitic infection.
PubMed: 38803639
DOI: 10.3389/fped.2024.1410850 -
Clinical Case Reports Jun 2024Among the multitude of causes for acute abdomen patients presenting with free intraperitoneal air, one almost never finds infected pancreatic necrosis as one of the...
KEY CLINICAL MESSAGE
Among the multitude of causes for acute abdomen patients presenting with free intraperitoneal air, one almost never finds infected pancreatic necrosis as one of the culprits. In patients with risk factors for acute pancreatitis presenting with generalized peritonitis with free intraperitoneal air, consideration should be given to this often deadly entity.
ABSTRACT
Acute pancreatitis is a morbid acute abdominal pathology that has been increasing in incidence in recent years. Most patients have a mild disease and treated medically, while a few proportion require interventional procedures. We present the case of a 39-year-old male patient who presented with progressive abdominal pain, vomiting, and yellowish discoloration of the eyes. The abdominal condition progressed to the point where clinical signs became consistent with generalized peritonitis and an x-ray finding of free intraperitoneal air. The patient underwent exploratory laparotomy with intraoperative findings of intraperitoneal rupture of infected pancreatic necrosis with intraperitoneal purulent collection. He was managed with necrosectomy and discharged improved after intensive care and general ward stay.
PubMed: 38803324
DOI: 10.1002/ccr3.8958 -
Renal Failure Dec 2024Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort...
Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, .010), and lower (each 1-absolute unit decrease) / values (95% CI 0.859-0.984, .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, = 35; non-sSHPT group, = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.
Topics: Humans; Male; Hyperparathyroidism, Secondary; Middle Aged; Retrospective Studies; Female; Peritoneal Dialysis; Prognosis; Risk Factors; Parathyroid Hormone; Adult; Kidney Failure, Chronic; Disease Progression; Proportional Hazards Models
PubMed: 38803195
DOI: 10.1080/0886022X.2024.2356022 -
Cureus Apr 2024Mesenteric cysts are mostly congenital cysts of varied etiology. They occur twice as often in females than in males. They have varied clinical presentations. Most of...
Mesenteric cysts are mostly congenital cysts of varied etiology. They occur twice as often in females than in males. They have varied clinical presentations. Most of them are asymptomatic, and a few present with abdominal mass, abdominal pain, nausea, and vomiting. Ultrasonography and computed tomography (CT) are essential in their diagnosis. These cysts may get complicated due to hemorrhage, torsion, rupture, or infection and may become life-threatening with features of acute abdominal pain and peritonitis. This is a case presentation of a 22-year-old Indian female who came with abdominal pain and was found to have an infected mesenteric cyst on laparotomy.
PubMed: 38800183
DOI: 10.7759/cureus.58975