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Microorganisms May 2024Spontaneous Bacterial Peritonitis (SBP) is a serious complication and a common cause of death in patients with liver cirrhosis. Between January 2017 and March 2024, a...
Spontaneous Bacterial Peritonitis (SBP) is a serious complication and a common cause of death in patients with liver cirrhosis. Between January 2017 and March 2024, a retrospective study was conducted involving 302 patients (>18 years old) with ascites treated at a tertiary referral center in south-eastern Poland. Microbiological analysis of the ascitic fluids was performed in all patients. The presence of microorganisms was found in samples from 17 patients, and 21 pathogens were isolated, including 15 Gram-positive bacteria and 6 Gram-negative bacteria. , MRCNS (methicillin-resistant coagulase-negative staphylococci, resistant to all beta-lactam antibiotics: penicillins, penicillins with beta-lactamase inhibitor, cephalosporins and carbapenems) was the main pathogen detected (19.05%, 4/21), followed by (9.52%, 2/21), (9.52%, 2/21), , MRCNS (4.76%, 1/21), (9.52%, 2/21), (9.52%, 2/21), (4.76%, 1/21) and spp. (4.76%, 1/21). The following Gram-negative bacteria were also found in the specimens examined: , ESBL (extended-spectrum β-lactamase producing ) (4.76%, 1/21), (4.76%, 1/21), (4.76%, 1/21), (9.52%, 2/21) and (4.76%, 1/21). Gram-positive bacteria caused nosocomial infections in nine patients with SBP, Gram-negative bacteria caused nosocomial infections in two patients. In six patients with SBP, community-acquired infections caused by Gram-negative bacteria were found in three cases, Gram-positive bacteria in two cases, and in one case, community-acquired infection was caused by mixed Gram-positive and Gram-negative. Bacteria isolated from patients with hospital-acquired SBP showed higher drug resistance than those found in patients with non-hospital SBP. Bacterial infections in cirrhotic patients with complications may be responsible for their deteriorating health. Prompt intervention is critical to reducing mortality.
PubMed: 38792837
DOI: 10.3390/microorganisms12051008 -
Genes Apr 2024Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained... (Review)
Review
INTRODUCTION
Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation.
CONCLUSIONS
This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.
Topics: Humans; Peritoneal Dialysis; Cell-Free Nucleic Acids; DNA, Mitochondrial; Biomarkers; MicroRNAs; DNA, Bacterial; Peritonitis; Peritoneum
PubMed: 38790182
DOI: 10.3390/genes15050553 -
Molecular Therapy : the Journal of the... May 2024Sepsis-associated encephalopathy (SAE) is a frequent complication of severe systemic infection resulting in delirium, premature death, and long-term cognitive...
Sepsis-associated encephalopathy (SAE) is a frequent complication of severe systemic infection resulting in delirium, premature death, and long-term cognitive impairment. We closely mimicked SAE in a murine peritoneal contamination and infection (PCI) model. We found long-lasting synaptic pathology in the hippocampus including defective long-term synaptic plasticity, reduction of mature neuronal dendritic spines, and severely affected excitatory neurotransmission. Genes related to synaptic signaling, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and members of the transcription-regulatory EGR gene family, were downregulated. At the protein level, ARC expression and mitogen-activated protein kinase signaling in the brain were affected. For targeted rescue we used adeno-associated virus-mediated overexpression of ARC in the hippocampus in vivo. This recovered defective synaptic plasticity and improved memory dysfunction. Using the enriched environment paradigm as a non-invasive rescue intervention, we found improvement of defective long-term potentiation, memory, and anxiety. The beneficial effects of an enriched environment were accompanied by an increase in brain-derived neurotrophic factor (BDNF) and ARC expression in the hippocampus, suggesting that activation of the BDNF-TrkB pathway leads to restoration of the PCI-induced reduction of ARC. Collectively, our findings identify synaptic pathomechanisms underlying SAE and provide a conceptual approach to target SAE-induced synaptic dysfunction with potential therapeutic applications to patients with SAE.
PubMed: 38788710
DOI: 10.1016/j.ymthe.2024.05.001 -
Antibiotics (Basel, Switzerland) Apr 2024The ESKAPE group (, , , , , spp.) is a group of bacteria very difficult to treat due to their high ability to acquire resistance to antibiotics and are the main cause...
Prevalence of Infections and Antimicrobial Resistance of ESKAPE Group Bacteria Isolated from Patients Admitted to the Intensive Care Unit of a County Emergency Hospital in Romania.
UNLABELLED
The ESKAPE group (, , , , , spp.) is a group of bacteria very difficult to treat due to their high ability to acquire resistance to antibiotics and are the main cause of nosocomial infections worldwide, posing a threat to global public health. Nosocomial infections with MDR bacteria are found mainly in Intensive Care Units, due to the multitude of maneuvers and invasive medical devices used, the prolonged antibiotic treatments, the serious general condition of these critical patients, and the prolonged duration of hospitalization.
MATERIALS AND METHODS
During a period of one year, from January 2023 to December 2023, this cross-sectional study was conducted on patients diagnosed with sepsis admitted to the Intensive Care Unit of the Sibiu County Emergency Clinical Hospital. Samples taken were tracheal aspirate, catheter tip, pharyngeal exudate, wound secretion, urine culture, blood culture, and peritoneal fluid.
RESULTS
The most common bacteria isolated from patients admitted to our Intensive Care Unit was , followed by and . Gram-positive cocci ( and ) were rarely isolated. Most of the bacteria isolated were MDR bacteria.
CONCLUSIONS
The rise of antibiotic and antimicrobial resistance among strains in the nosocomial environment and especially in Intensive Care Units raises serious concerns about limited treatment options.
PubMed: 38786129
DOI: 10.3390/antibiotics13050400 -
BMC Pediatrics May 2024To compare the clinical characteristics, surgical management and prognosis of mesenteric lymphatic malformations (ML) and omental lymphatic malformations (OL) in...
PURPOSE
To compare the clinical characteristics, surgical management and prognosis of mesenteric lymphatic malformations (ML) and omental lymphatic malformations (OL) in children.
METHODS
This retrospective study included 148 ML patients and 53 OL patients who underwent surgical treatment at two centers between January 2016 and December 2022. Details about the patients' clinical characteristics, cyst characteristics, preoperative complications, surgical methods, and prognosis were retrieved and compared.
RESULTS
No significant differences in sex ratio, prenatal diagnosis, or age of diagnosis were noted between ML and OL patients. Vomiting was more common in ML patients than in OL patients (46.6% vs. 22.6%, P = 0.002), but OL patients were more likely to be misdiagnosed (35.8% vs. 18.9%, P = 0.012). The size of the cysts in OL patients was significantly larger than that in ML patients (14.0 [4.0-30.0] vs. 10.0 [2.0-50.0] cm, P<0.001), and cysts with turbid fluid were more common in OL patients (38.0% vs. 20.6%, P<0.001). More OL patients than ML patients had preoperative hemorrhage or infection of cysts (41.5% vs. 31.8%, P<0.016). Cyst excision was performed in 137 (92.6%) ML patients and 51 (96.2%) OL patients, and the incidence of postoperative complications was lower (12.6% vs. 4.2%, P = 0.165) among OL patients. The main postoperative complications included adhesive ileus and recurrence of cysts. Additionally, more OL patients than ML patients were treated with laparoscopic surgery (69.8% vs. 39.2%, P<0.001).
CONCLUSIONS
There were differences in clinical characteristics, cyst characteristics and preoperative complications between ML and OL patients. Cyst excision was the most common surgical method that was used to treat both ML and OL patients, and laparoscopic surgery could be a feasible surgical approach for treating OL patients with a good prognosis.
TRIAL REGISTRATION
Retrospectively registered.
Topics: Humans; Retrospective Studies; Male; Female; Omentum; Infant; China; Child, Preschool; Lymphatic Abnormalities; Mesentery; Child; Postoperative Complications; Prognosis; Infant, Newborn
PubMed: 38783260
DOI: 10.1186/s12887-024-04808-w -
JCI Insight May 2024DC inhibitory receptor (DCIR) is a C-type lectin receptor selectively expressed on myeloid cells, including monocytes, macrophages, DCs, and neutrophils. Its role in...
DC inhibitory receptor (DCIR) is a C-type lectin receptor selectively expressed on myeloid cells, including monocytes, macrophages, DCs, and neutrophils. Its role in immune regulation has been implicated in murine models and human genome-wide association studies, suggesting defective DCIR function associates with increased susceptibility to autoimmune diseases such as rheumatoid arthritis, lupus, and Sjögren's syndrome. However, little is known about the mechanisms underlying DCIR activation to dampen inflammation. Here, we developed anti-DCIR agonistic antibodies that promote phosphorylation on DCIR's immunoreceptor tyrosine-based inhibitory motifs and recruitment of SH2 containing protein tyrosine phosphatase-2 for reducing inflammation. We also explored the inflammation resolution by depleting DCIR+ cells with antibodies. Utilizing a human DCIR-knock-in mouse model, we validated the antiinflammatory properties of the agonistic anti-DCIR antibody in experimental peritonitis and colitis. These findings provide critical evidence for targeting DCIR to develop transformative therapies for inflammatory diseases.
Topics: Animals; Mice; Humans; Signal Transduction; Inflammation; Peritonitis; Disease Models, Animal; Colitis; Phosphorylation; Mice, Inbred C57BL
PubMed: 38781017
DOI: 10.1172/jci.insight.176064 -
Frontiers in Immunology 2024Peritoneal dialysis is a widely used method for treating kidney failure. However, over time, the peritoneal structure and function can deteriorate, leading to the... (Review)
Review
Peritoneal dialysis is a widely used method for treating kidney failure. However, over time, the peritoneal structure and function can deteriorate, leading to the failure of this therapy. This deterioration is primarily caused by infectious and sterile inflammation. Sterile inflammation, which is inflammation without infection, is particularly concerning as it can be subtle and often goes unnoticed. The onset of sterile inflammation involves various pathological processes. Peritoneal cells detect signals that promote inflammation and release substances that attract immune cells from the bloodstream. These immune cells contribute to the initiation and escalation of the inflammatory response. The existing literature extensively covers the involvement of different cell types in the sterile inflammation, including mesothelial cells, fibroblasts, endothelial cells, and adipocytes, as well as immune cells such as macrophages, lymphocytes, and mast cells. These cells work together to promote the occurrence and progression of sterile inflammation, although the exact mechanisms are not fully understood. This review aims to provide a comprehensive overview of the signals from both stromal cells and components of immune system, as well as the reciprocal interactions between cellular components, during the initiation of sterile inflammation. By understanding the cellular and molecular mechanisms underlying sterile inflammation, we may potentially develop therapeutic interventions to counteract peritoneal membrane damage and restore normal function.
Topics: Humans; Peritoneal Dialysis; Peritoneum; Animals; Stromal Cells; Cell Communication; Inflammation; Peritonitis
PubMed: 38779674
DOI: 10.3389/fimmu.2024.1387292 -
Frontiers in Immunology 2024Sepsis remains a major source of morbidity and mortality in neonates, and characterization of immune regulation in the neonatal septic response remains limited. HVEM is...
INTRODUCTION
Sepsis remains a major source of morbidity and mortality in neonates, and characterization of immune regulation in the neonatal septic response remains limited. HVEM is a checkpoint regulator which can both stimulate or inhibit immune responses and demonstrates altered expression after sepsis. We hypothesized that signaling via HVEM would be essential for the neonatal response to sepsis, and that therefore blockade of this pathway would improve survival to septic challenge.
METHODS
To explore this, neonatal mice were treated with cecal slurry (CS), CS with Anti-HVEM antibody (CS-Ab) or CS with isotype (CS-IT) and followed for 7-day survival. Mice from all treatment groups had thymus, lung, kidney and peritoneal fluid harvested, weighed, and stained for histologic evaluation, and changes in cardiac function were assessed with echocardiography.
RESULTS
Mortality was significantly higher for CS-Ab mice (72.2%) than for CS-IT mice (22.2%). CS resulted in dysregulated alveolar remodeling, but CS-Ab lungs demonstrated significantly less dysfunctional alveolar remodeling than CS alone (MCL 121.0 CS vs. 87.6 CS-Ab), as well as increased renal tubular vacuolization. No morphologic differences in alveolar septation or thymic karyorrhexis were found between CS-Ab and CS-IT. CS-Ab pups exhibited a marked decrease in heart rate (390.3 Sh vs. 342.1 CS-Ab), stroke volume (13.08 CS-IT vs. 8.83 CS-Ab) and ultimately cardiac output (4.90 Sh vs. 3.02 CS-Ab) as well as a significant increase in ejection fraction (73.74 Sh vs. 83.75 CS-Ab) and cardiac strain (40.74 Sh vs. 51.16 CS-Ab) as compared to CS-IT or Sham animals.
DISCUSSION
While receptor ligation of aspects of HVEM signaling, via antibody blockade, appears to mitigate aspects of lung injury and thymic involution, stimulatory signaling via HVEM still seems to be necessary for vascular and hemodynamic resilience and overall neonatal mouse survival in response to this experimental polymicrobial septic insult. This dissonance in the activity of anti-HVEM neutralizing antibody in neonatal animals speaks to the differences in how septic cardiac dysfunction should be considered and approached in the neonatal population.
Topics: Animals; Mice; Animals, Newborn; Signal Transduction; Neonatal Sepsis; Receptors, Tumor Necrosis Factor, Member 14; Disease Models, Animal; Female; Heart Diseases; Lung; Sepsis
PubMed: 38774873
DOI: 10.3389/fimmu.2024.1365174 -
Antimicrobial Stewardship & Healthcare... 2024This study aimed to investigate and contain a cluster of invasive candidiasis cases caused by fluconazole-resistant (FRC) in a neonatal intensive care unit.
OBJECTIVE
This study aimed to investigate and contain a cluster of invasive candidiasis cases caused by fluconazole-resistant (FRC) in a neonatal intensive care unit.
METHODS
Active surveillance was initiated. Direct observations of hand-hygiene compliance (HHC) among staff were conducted before and after the implementation of hand-hygiene (HH) education. Thirty-five environmental cultures were obtained. Phylogenetic analysis of FRC was performed using Fourier-transform infrared spectroscopy and microsatellite genotyping.
RESULTS
A total of 14 patients (mean birth weight = 860 g, gestational age = 25 weeks) infected with FRC were identified using the fully automated analyzer, including 5 with clinical infection (three with catheter-related bloodstream infection, one with cutaneous infection, and one with fatal peritonitis) and 9 with colonization. The HHC rate in nurses before performing a sterile or aseptic procedure significantly improved after the HH education ( < .05). Sinks near the patients were contaminated with FRC. All FRC strains were confirmed to be susceptible to fluconazole using the CLSI method, and the microdilution procedure indicated a trailing effect. Phylogenetic analysis showed that all the fluconazole-trailing isolates from patients were clustered together and had the same genotype. Sinks were successfully decontaminated using accelerated hydrogen peroxide and drainage pipes were replaced. Ultraviolet-C decontamination was applied in the milk preparation room. No new cases were detected after the education and disinfection interventions.
CONCLUSIONS
Sinks are an important reservoir of . Active surveillance, environmental hygiene, and constant staff education on maintaining a high level of HHC are necessary to limit the spread of .
PubMed: 38774118
DOI: 10.1017/ash.2024.77 -
AIDS Research and Therapy May 2024Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual...
INTRODUCTION
Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited.
METHODS
A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg. He underwent serial blood plasma, peripheral blood mononuclear cell, and urine PK measurements over 24 h after an observed DTG + FTC/TAF dose.
RESULTS
Plasma trough (Cmin) concentrations of TAF, tenofovir (TFV), FTC, and DTG were 0.05, 164, 1,006, and 718 ng/mL, respectively. Intracellular trough concentrations of TFV-DP and FTC-TP were 1142 and 11,201 fmol/million cells, respectively. Compared to published mean trough concentrations in PWH with normal kidney function, observed TFV and FTC trough concentrations were 15.5- and 20-fold higher, while intracellular trough concentrations of TFV-DP and FTC-TP were 2.2-fold and 5.4-fold higher, respectively. TFV and FTC urine levels were 20 times lower than in people with normal GFR.
CONCLUSIONS
In a single ESKD PWH on PD, daily TAF was associated with plasma TFV and intracellular TFV-DP trough concentrations 15-fold and 2-fold higher than those of people with uncompromised kidney function, potentially contributing to nephrotoxicity. This suggests that TFV accumulates on PD; thus, daily TAF in PD patients may require dose adjustment or regimen change to optimize treatment, minimize toxicity, and preserve residual kidney function.
Topics: Humans; Male; Heterocyclic Compounds, 3-Ring; Oxazines; Pyridones; Middle Aged; Tenofovir; Emtricitabine; Peritoneal Dialysis; Piperazines; HIV Infections; Anti-HIV Agents; Alanine; Adenine; Kidney Failure, Chronic
PubMed: 38773606
DOI: 10.1186/s12981-024-00616-5