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Chinese Journal of Cancer Research =... Feb 2024Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence...
OBJECTIVE
Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.
METHODS
In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.
RESULTS
Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. and were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0).
CONCLUSIONS
There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.
PubMed: 38455368
DOI: 10.21147/j.issn.1000-9604.2024.01.07 -
Cureus Aug 2023Peritonitis is inflammation of the peritoneum that can arise from a number of complications affecting the lining of the abdominal wall and organs. Acute abdomen and...
Peritonitis is inflammation of the peritoneum that can arise from a number of complications affecting the lining of the abdominal wall and organs. Acute abdomen and peritonitis is a rare complication in a previously healthy woman following a seemingly uncomplicated normal full-term vaginal delivery. We report such a case in a 20-year-old gravida 2 para 2 (G2P2) woman of Guatemalan descent, who presented nine days postpartum following an uncomplicated delivery, to the emergency room with acute abdomen and associated systemic inflammatory reaction. Interventional radiology paracentesis was performed, yielding a milky, purulent peritoneal fluid with no visible organisms and negative cultures. Antibiotics and paracentesis were insufficient in managing her condition, which continued to worsen over the course of several days. Given her continued deterioration despite clinical intervention, she underwent an exploratory laparotomy and peritoneal lavage along with continued broad-spectrum antibiotics. Cultures continued to be negative but operative findings included diffuse fibrinous peritonitis with no obvious abscess or perforated abdominal viscus. Following surgical laparotomy, she recovered fully without any complications. We review the available literature regarding peritonitis, discuss its management, and speculate as to its cause in this case.
PubMed: 37701003
DOI: 10.7759/cureus.43339 -
Updates in Surgery Aug 2023The aim of this study is to define the importance of peritoneal CEA (pCEA) as a prognostic factor of overall survival (OS) and disease-free survival (DFS) in gastric...
The aim of this study is to define the importance of peritoneal CEA (pCEA) as a prognostic factor of overall survival (OS) and disease-free survival (DFS) in gastric cancer (GC) patients surgically treated with a curative intent In our department. A total of 64 patients affected by gastric cancer with intraoperatively measurement of CEA on peritoneal lavage were enrolled in the study. Patients were divided into two groups: (A) the peritoneal lavage CEA ( -) with CEA < 0.5 ng/ml and (B) the peritoneal lavage CEA ( +) with CEA ≥ 0.5 ng/ml. Then we analyzed OS and DFS of the two groups correlating them to others clinico-pathological features. Furthermore, we investigated the correlation between pCEA and peritoneal cytology. We demonstrated a strong significant difference in OS and in DFS in CEA ( +) patients. We emphasized that pCEA had a strong survival impact, in both OS and DFS, in selected patients affected by diffuse histotype GC (p = 0.0048 and p = 0.0030 respectively), stage III (p = 0.015 and p = 0.021, respectively) and distal gastric cancer (p = 0.0036 and p = 0.0017, respectively). There is a strong need to recognize prognostic factors that can help clinicians to stratify patients at high risk to develop post-surgical recurrences and moreover to recognize who could benefit from an aggressive surgical treatment of cytoreductive surgery and intra-peritoneal chemotherapy.pCEA is a good predictor of survival in advanced gastric cancer and could discriminate which patients need a more accurate follow-up program and an intensive therapeutic strategy.
Topics: Humans; Carcinoembryonic Antigen; Prognosis; Stomach Neoplasms; Peritoneal Lavage; Peritoneum
PubMed: 37347355
DOI: 10.1007/s13304-023-01542-3 -
Scientific Reports Feb 2024Extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) are pivotal bioactive structures involved in various processes including inflammation. Herein we...
Extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) are pivotal bioactive structures involved in various processes including inflammation. Herein we report the interactions between EVs and NETs during murine endotoxemia studied in situ directly in the vasculature (cremaster muscle, liver sinusoids) using intravital microscopy (IVM). We captured NETs and EV release in real time by both non- and polarized neutrophils in liver but not in cremaster vasculature. When comparing numbers of circulating EVs of various origin (nanoparticle tracking analysis-NTA, flow cytometry) with those interacting with endothelium and NETs (IVM) we observed that whereas platelet and monocyte/macrophage-derived EVs dominate in blood and peritoneal lavage, respectively, mostly neutrophil-derived EVs interact with the vascular lining, NETs and leukocytes. Despite the interaction, NETs do not affect EV formation as NET release inhibition did not alter EV release. However, EVs inhibit NETs formation and in particular, erythrocyte-derived EVs downregulate NET release and this effect is mediated via Siglec-E-dependent interactions with neutrophils. Overall, we report that EVs are present in NETs in vivo and they do modulate their release but the process in not bidirectional. Moreover, EVs isolated from body fluids might not reflect their importance in direct endothelial- and leukocyte-related interactions.
Topics: Mice; Animals; Extracellular Traps; Neutrophils; Inflammation; Leukocytes; Extracellular Vesicles
PubMed: 38409254
DOI: 10.1038/s41598-024-55081-x -
The American Surgeon Oct 2023Some reports suggest Diagnostic peritoneal aspiration (DPA) or lavage (DPL) may better select which hypotensive blunt trauma patients (BTPs) require operation, compared...
BACKGROUND
Some reports suggest Diagnostic peritoneal aspiration (DPA) or lavage (DPL) may better select which hypotensive blunt trauma patients (BTPs) require operation, compared to ultrasonography. However, whether both moderately hypotensive (systolic blood pressure [SBP] < 90 mmHg) and severely hypotensive (SBP < 70 mmHg) patients benefit from DPA/DPL is unclear. We hypothesized DPA/DPL used within the first hour increases risk of death for severely vs moderately hypotensive BTPs.
METHODS
The 2017-2019 Trauma Quality Improvement Program database was queried for BTPs ≥ 18 years old with hypotension upon arrival. We compared moderately and severely hypotensive groups. A multivariable logistic regression analysis was performed controlling for age, comorbidities, emergent operation, blood transfusions, and injury profile.
RESULTS
From 134 hypotensive patients undergoing DPA/DPL, 66 (49.3%) had severe hypotension. Patients in both groups underwent an emergent operation (43.9% vs 58.8%, = .09) in a similar amount of time (median, 42-min vs 54-min, = .11). Compared to the moderately hypotensive group, severely hypotensive patients had a higher rate and associated risk of death (84.8% vs 50.0%, < .001) (OR 5.40, CI 2.07-14.11, < .001). The strongest independent risk factor for death was age ≥ 65 (OR 24.81, CI 4.06-151.62, < .001).
DISCUSSION
Among all BTPs undergoing DPA/DPL within the first hour of arrival, an over 5-fold increased risk of death for patients with severe hypotension was demonstrated. As such, DPA/DPL within this group should be used with caution, particularly for older patients, as they may be better served by immediate surgeries. Future prospective research is needed to confirm these findings and elucidate the ideal DPA/DPL population in the modern era of ultrasonography.
Topics: Humans; Adolescent; Abdominal Injuries; Peritoneal Lavage; Peritoneum; Wounds, Nonpenetrating; Hypotension
PubMed: 37154296
DOI: 10.1177/00031348231175132 -
Journal of Infection and Public Health May 2024The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species...
BACKGROUND
The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited.
METHODS
This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source.
RESULTS
Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively.
CONCLUSIONS
This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.
Topics: Animals; Humans; Male; Female; Adult; Middle Aged; Aged; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Mycobacterium tuberculosis; Mycobacterium leprae; Panama; Tuberculosis; HIV Infections
PubMed: 38518684
DOI: 10.1016/j.jiph.2024.03.004 -
Scientific Reports May 2024Endothelial glycocalyx (eGC) covers the inner surface of the vessels and plays a role in vascular homeostasis. Syndecan is considered the "backbone" of this structure....
Endothelial glycocalyx (eGC) covers the inner surface of the vessels and plays a role in vascular homeostasis. Syndecan is considered the "backbone" of this structure. Several studies have shown eGC shedding in sepsis and its involvement in organ dysfunction. Matrix metalloproteinases (MMP) contribute to eGC shedding through their ability for syndecan-1 cleavage. This study aimed to investigate if doxycycline, a potent MMP inhibitor, could protect against eGC shedding in lipopolysaccharide (LPS)-induced sepsis and if it could interrupt the vascular hyperpermeability, neutrophil transmigration, and microvascular impairment. Rats that received pretreatment with doxycycline before LPS displayed ultrastructural preservation of the eGC observed using transmission electronic microscopy of the lung and heart. In addition, these animals exhibited lower serum syndecan-1 levels, a biomarker of eGC injury, and lower perfused boundary region (PBR) in the mesenteric video capillaroscopy, which is inversely related to the eGC thickness compared with rats that only received LPS. Furthermore, this study revealed that doxycycline decreased sepsis-related vascular hyperpermeability in the lung and heart, reduced neutrophil transmigration in the peritoneal lavage and inside the lungs, and improved some microvascular parameters. These findings suggest that doxycycline protects against LPS-induced eGC shedding, and it could reduce vascular hyperpermeability, neutrophils transmigration, and microvascular impairment.
Topics: Glycocalyx; Animals; Sepsis; Doxycycline; Rats; Male; Lipopolysaccharides; Capillary Permeability; Lung; Syndecan-1; Rats, Wistar; Endothelium, Vascular; Endothelial Cells; Neutrophils; Matrix Metalloproteinase Inhibitors
PubMed: 38714743
DOI: 10.1038/s41598-024-60919-5 -
Frontiers in Immunology 2024Sepsis is one of the major causes of death and increased health care burden in modern intensive care units. Immune checkpoints have been prompted to be key modulators of...
BACKGROUND
Sepsis is one of the major causes of death and increased health care burden in modern intensive care units. Immune checkpoints have been prompted to be key modulators of T cell activation, T cell tolerance and T cell exhaustion. This study was designed to investigate the role of the negative immune checkpoint, T cell immunoglobulin and ITIM domain (TIGIT), in the early stage of sepsis.
METHOD
An experimental murine model of sepsis was developed by cecal ligation and puncture (CLP). TIGIT and CD155 expression in splenocytes at different time points were assessed using flow cytometry. And the phenotypes of TIGIT-deficient (TIGIT) and wild-type (WT) mice were evaluated to explore the engagement of TIGIT in the acute phase of sepsis. In addition, the characteristics were also evaluated in the WT septic mice pretreated with anti-TIGIT antibody. TIGIT and CD155 expression in tissues was measured using real-time quantitative PCR and immunofluorescence staining. Proliferation and effector function of splenic immune cells were evaluated by flow cytometry. Clinical severity and tissue injury were scored to evaluate the function of TIGIT on sepsis. Additionally, tissue injury biomarkers in peripheral blood, as well as bacterial load in peritoneal lavage fluid and liver were also measured.
RESULTS
The expression of TIGIT in splenic T cells and NK cells was significantly elevated at 24 hours post CLP.TIGIT and CD155 mRNA levels were upregulated in sepsis-involved organs when mice were challenged with CLP. In CLP-induced sepsis, CD4 T cells from TIGIT mice shown increased proliferation potency and cytokine production when compared with that from WT mice. Meanwhile, innate immune system was mobilized in TIGIT mice as indicated by increased proportion of neutrophils and macrophages with potent effector function. In addition, tissue injury and bacteria burden in the peritoneal cavity and liver was reduced in TIGIT mice with CLP induced sepsis. Similar results were observed in mice treated with anti-TIGIT antibody.
CONCLUSION
TIGIT modulates CD4 T cell response against polymicrobial sepsis, suggesting that TIGIT could serve as a potential therapeutic target for sepsis.
Topics: Animals; Mice; CD4-Positive T-Lymphocytes; Killer Cells, Natural; Receptors, Immunologic; Sepsis; T-Lymphocytes
PubMed: 38545097
DOI: 10.3389/fimmu.2024.1290564 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Jun 2024This study evaluated the use of metformin or pioglitazone in preventing or reducing the development of post-operative intra-abdominal adhesion (PIAA) by employing...
BACKGROUND
This study evaluated the use of metformin or pioglitazone in preventing or reducing the development of post-operative intra-abdominal adhesion (PIAA) by employing histopathological, immunohistochemical, and biochemical analyses in an experimental adhesion model.
METHODS
Fifty Wistar-Albino rats were divided into five groups: Group I (Control), Group II (Sham Treatment), Group III (Hy-aluronic Acid), Group IV (Metformin), and Group V (Pioglitazone). Adhesions were induced in the experimental groups, except for the sham group, using the scraping method. After 10 days, rats were euthanized for evaluation. Macroscopic adhesion degrees were assessed using Nair's scoring system. Immunohistochemical and enzyme-linked immunosorbent assay (ELISA) methods were utilized to assess serum, peritoneal lavage, and intestinal tissue samples. Fructosamine, interleukin-6 (IL-6), transforming growth factor-beta (TGF-β), and fibronectin levels were measured in serum and peritoneal lavage samples.
RESULTS
The groups exhibited similar Nair scores and Type I or Type III Collagen staining scores (all, p>0.05). Pioglitazone significantly reduced serum IL-6 and TGF-β levels compared to controls (p=0.002 and p=0.008, respectively). Both metformin and pioglitazone groups showed elevated IL-6 in peritoneal lavage relative to controls, while fibronectin levels in the lavage were lower in pioglitazone-treated rats compared to the sham group (all, p<0.005).
CONCLUSION
Pioglitazone, but not metformin, demonstrated a positive biochemical impact on preventing PIAA formation in an experimental rat model, although histological impacts were not observed. Further experimental studies employing different dose/duration regimens of pioglitazone are needed to enhance our understanding of its effect on PIAA formation.
Topics: Animals; Pioglitazone; Metformin; Tissue Adhesions; Rats, Wistar; Rats; Disease Models, Animal; Hypoglycemic Agents; Male; Thiazolidinediones; Postoperative Complications
PubMed: 38863295
DOI: 10.14744/tjtes.2024.61732 -
Theranostics 2024A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured...
Lipid nanoparticle encapsulated large peritoneal macrophages migrate to the lungs via the systemic circulation in a model of clodronate-mediated lung-resident macrophage depletion.
A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured tissues and impart wound healing properties. Here, we sought to expand on this unique ability of large peritoneal macrophages (LPMs) by investigating whether these GATA6+ LPMs could also intravasate into systemic circulation and migrate to extra-peritoneally located lungs upon ablating lung-resident alveolar macrophages (AMs) by intranasally administered clodronate liposomes in mice. C12-200 cationic lipidoid-based nanoparticles were employed to selectively deliver a small interfering RNA (siRNA)-targeting CD-45 labeled with a cyanine 5.5 (Cy5.5) dye to LPMs via intraperitoneal injection. We utilized a non-invasive optical technique called Diffuse Flow Cytometry (DiFC) to then systemically track these LPMs in real time and paired it with more conventional techniques like flow cytometry and immunocytochemistry to initially confirm uptake of C12-200 encapsulated siRNA-Cy5.5 (siRNA-Cy5.5 (C12-200)) into LPMs, and further track them from the peritoneal cavity to the lungs in a mouse model of AM depletion incited by intranasally administered clodronate liposomes. Also, we stained for LPM-specific marker zinc-finger transcription factor GATA6 in harvested cells from biofluids like broncho-alveolar lavage as well as whole blood to probe for Cy5.5-labeled LPMs in the lungs as well as in systemic circulation. siRNA-Cy5.5 (C12-200) was robustly taken up by LPMs. Upon depletion of lung-resident AMs, these siRNA-Cy5.5 (C12-200) labeled LPMs rapidly migrated to the lungs via systemic circulation within 12-24 h. DiFC results showed that these LPMs intravasated from the peritoneal cavity and utilized a systemic route of migration. Moreover, immunocytochemical staining of zinc-finger transcription factor GATA6 further confirmed results from DiFC and flow cytometry, confirming the presence of siRNA-Cy5.5 (C12-200)-labeled LPMs in the peritoneum, whole blood and BALF only upon clodronate-administration. Our results indicate for the very first time that selective tropism, migration, and infiltration of LPMs into extra-peritoneally located lungs was dependent on clodronate-mediated AM depletion. These results further open the possibility of therapeutically utilizing LPMs as delivery vehicles to carry nanoparticle-encapsulated oligonucleotide modalities to potentially address inflammatory diseases, infectious diseases and even cancer.
Topics: Animals; Clodronic Acid; Nanoparticles; Mice; Lung; Macrophages, Peritoneal; Macrophages, Alveolar; RNA, Small Interfering; GATA6 Transcription Factor; Liposomes; Mice, Inbred C57BL; Carbocyanines; Cell Movement; Flow Cytometry
PubMed: 38646640
DOI: 10.7150/thno.91062