-
Cancers May 2024Bromodomain and extra-terminal (BET) domain proteins that bind to acetylated lysine residues of histones serve as the "readers" of DNA acetylation. BRD4 is the most...
BACKGROUND
Bromodomain and extra-terminal (BET) domain proteins that bind to acetylated lysine residues of histones serve as the "readers" of DNA acetylation. BRD4 is the most thoroughly studied member of the BET family and regulates the expression of key oncogenes. BRD4 gene amplification has been identified in ovarian cancer (~18-19%) according to (TCGA) analysis. BET inhibitors are novel small molecules that displace BET proteins from acetylated histones and are currently tested in Phase I/II trials. We here aim to explore the prognostic role of the BRD4 gene and protein expression in the ascitic fluid of patients with advanced FIGO III/IV high-grade serous ovarian carcinoma (HGSC).
METHODS
Ascitic fluid was obtained from 28 patients with advanced stage (FIGO III/IV) HGSC through diagnostic/therapeutic paracentesis or laparoscopy before the initiation of chemotherapy. An amount of ~200 mL of ascitic fluid was collected from each patient and peripheral blood mononuclear cells () were isolated. Each sample was evaluated for BRD4 and GAPDH gene expression through RT-qPCR and BRD4 protein levels through enzyme-linked immunosorbent assay (ELISA). The study protocol was approved by the Institutional Review Board of Alexandra University Hospital and the Committee on Ethics and Good Practice (CEGP) of the National and Kapodistrian University of Athens (NKUA).
RESULTS
Low BRD4 gene expression was associated with worse prognosis at 12 months compared to intermediate/high expression (95% CI; 1.75-30.49; = 0.008). The same association was observed at 24 months although this association was not statistically significant (95% CI; 0.96-9.2; = 0.065). Progression-free survival was shorter in patients with low BRD4 gene expression at 12 months (5.6 months; 95% CI; 2.6-8.6) compared to intermediate/high expression (9.8 months; 95% CI; 8.3-11.3) (95% CI; 1.2-16.5; = 0.03). The same association was confirmed at 24 months (6.9 months vs. 13.1 months) (95% CI; 1.1-8.6; = 0.048). There was a trend for worse prognosis in patients with high BRD4 protein levels versus intermediate/low BRD4 protein expression both at 12 months (9.8 months vs. 7.6 months; = 0.3) and at 24 months (14.2 months vs. 16.6 months; = 0.56) although not statistically significant. Again, there was a trend for shorter PFS in patients with high BRD4 protein expression although not statistically significant both at 12 months ( = 0.29) and at 24 months ( = 0.47).
CONCLUSIONS
There are contradictory data in the literature over the prognostic role of BRD4 gene expression in solid tumors. In our study, intermediate/high BRD4 gene expression was associated with a favorable prognosis in terms of overall survival and progression-free survival compared to low BRD4 gene expression.
PubMed: 38893083
DOI: 10.3390/cancers16111962 -
The American Surgeon Jun 2024Peritoneal adhesion is a common cause of small bowel obstruction (SBO). In this study, we included 40 adult patients who had SBO, or partial obstructive symptoms. In the...
Peritoneal adhesion is a common cause of small bowel obstruction (SBO). In this study, we included 40 adult patients who had SBO, or partial obstructive symptoms. In the abdominal instillation of crystalloid fluid (AICF) cohort, 16 patients underwent lysis of adhesions and abdominal crystalloid fluid instillation at the end of the procedure. In the control (CO) group, 24 patients received lysis of adhesions without fluid instillation. AICF was achieved by the abdominal instillation of 1864 ± 97.5 mL of crystalloid fluid. We analyzed the recurrence of peritoneal adhesions resulting in reoperation for SBO within the 64.3 ± 9.15 months of follow-up time for the CO and the 70.5 ± 13.16-month follow-up for the AICF group. The AICF group had a lower SBO recurrence rate of 12.5% compared to the CO group's 41.6% rate ( = .049). Taken together, AICF decreased the recurrence of SBO requiring reoperation secondary to adhesion formation compared to the lysis of adhesions alone, as seen in the CO group.
PubMed: 38884650
DOI: 10.1177/00031348241262426 -
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 -
The Pan African Medical Journal 2024Acute chylous peritonitis is an uncommon medical condition that can occur suddenly, resulting in the buildup of chylous fluid in the peritoneal cavity. It is considered... (Review)
Review
Acute chylous peritonitis is an uncommon medical condition that can occur suddenly, resulting in the buildup of chylous fluid in the peritoneal cavity. It is considered idiopathic because the exact cause is often unknown. The symptoms of acute chylous idiopathic peritonitis can mimic other abdominal emergencies, making it challenging to diagnose and manage, requiring a multidisciplinary approach. We present a case report of acute idiopathic chylous peritonitis miming acute abdomen, how was successfully treated with surgery, and provide a comprehensive review of the available literature on this topic. Chylous peritonitis is a rare condition whose clinical presentation mimics an acute abdomen. It is necessary to undertake careful exploration. An emergent laparotomy is indicated to treat the peritonitis and search for and treat the underlying cause.
Topics: Humans; Abdomen, Acute; Acute Disease; Chylous Ascites; Diagnosis, Differential; Laparotomy
PubMed: 38881770
DOI: 10.11604/pamj.2024.47.131.42794 -
Mycopathologia Jun 2024A 67 year-old male was admitted in the ICU because of multi-organ failure due to sepsis secondary to Fournier's gangrene. He had sustained radical prostatectomy in the...
A 67 year-old male was admitted in the ICU because of multi-organ failure due to sepsis secondary to Fournier's gangrene. He had sustained radical prostatectomy in the last 48 hours. Peritoneal fluid and fatty tissue biopsies grew Aspergillus Fumigatus without concomitant pulmonary involvement. Postoperative acquisition via exogenous and endogenous routes is discussed, as this nosocomial entity is very rarely reported apart from peritoneal dialysis, especially in non-immunosuppressed patients.
Topics: Humans; Male; Aspergillus fumigatus; Aged; Peritonitis; Aspergillosis; Postoperative Complications; Prostatectomy
PubMed: 38878212
DOI: 10.1007/s11046-024-00858-x -
BMC Women's Health Jun 2024
PubMed: 38877538
DOI: 10.1186/s12905-024-03194-w -
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 -
International Journal of Reproductive... Mar 2023Endometriosis is a chronic estrogen-related inflammatory disorder that is known by proliferating endometrial cells in a place outside the uterus. The high presence of...
Human V 7.2-J 33 mucosal-associated invariant T cells in endometrial ectopic tissues tend to produce interferon-gamma: A new player in endometriosis etiology: A case-control study.
BACKGROUND
Endometriosis is a chronic estrogen-related inflammatory disorder that is known by proliferating endometrial cells in a place outside the uterus. The high presence of immune cells in the peritoneal fluid of women with endometriosis confirms the involvement of the immune system in the pathogenesis of the disease. Mucosal-associated invariant T (MAIT) cells play an undeniable impact on mucosal immunity by the production of interleukin-17, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha. The function of the cells in the pathogenesis of endometriosis is less investigated.
OBJECTIVE
This study aims to investigate the infiltration of MAIT cells by using the determination levels of gene expression in eutopic and ectopic tissue of endometriosis lesions.
MATERIALS AND METHODS
In this case-control study, the tested samples include 20 eutopic and 20 ectopic tissues of women with endometriosis and 20 uterine endometrial tissues of women in the control group. Expressions of the tumor necrosis factor-alpha, interleukin-17A, and -γ genes were analyzed by quantitative reverse transcriptase-polymerase chain reaction.
RESULTS
According to the results, gene expression did not show substantial elevation in the uterine and eutopic endometrial tissues compared to internal gene control as well as in ectopic tissues. Correlation analysis approved a positive relationship between expression genes and -γ levels in ectopic tissues.
CONCLUSION
Considering the low-expression specific gene of MAIT cells in ectopic tissue, it can be concluded that these cells are present in the endometriotic environment to a certain extent, and there is a possibility of their role in the progression of endometriosis by secreting IFN- .
PubMed: 38868448
DOI: 10.18502/ijrm.v22i3.16168 -
CNS Oncology Jun 2024Primary effusion lymphoma (PEL) is an uncommon B-cell lymphoma associated with human herpesvirus 8 and comprises 3-4% of all HIV-related lymphomas. It traditionally...
Primary effusion lymphoma (PEL) is an uncommon B-cell lymphoma associated with human herpesvirus 8 and comprises 3-4% of all HIV-related lymphomas. It traditionally presents as a pleural, pericardial, and/or peritoneal effusion, though it can occasionally manifest as an extracavitary or solid mass in the absence of an effusion. The extracavitary or solid variant of primary effusion lymphoma has been reported in the skin, gastrointestinal tract, lung, and lymph nodes. However, very few cases have been reported in the central nervous system. We describe a case of extracavitary or solid variant of primary effusion lymphoma presenting as a brain mass in an HIV-positive man, highlighting the clinicopathologic and immunophenotypic findings of a rare entity.
Topics: Humans; Lymphoma, Primary Effusion; Male; Brain Neoplasms; Middle Aged
PubMed: 38864818
DOI: 10.1080/20450907.2024.2357535 -
Surgery Jun 2024Polymerase chain reaction is a method to detect bacterial DNA and is widely used because it delivers results within a few hours with the potential to guide postoperative...
BACKGROUND
Polymerase chain reaction is a method to detect bacterial DNA and is widely used because it delivers results within a few hours with the potential to guide postoperative antibiotic treatment. This study aims to determine if polymerase chain reaction can accurately detect bacteria in the peritoneal fluid compared with conventional culture from patients operated for acute appendicitis.
METHODS
This prospective cohort study included patients above the age of 18 years who underwent laparoscopic surgery for acute appendicitis. Peritoneal samples were collected before the appendectomy procedure for conventional culture and polymerase chain reaction using the BioFire Blood Culture Identification 2 Panel for comparison. During surgery, the surgeon assessed the appendicitis as either complicated or noncomplicated.
RESULTS
Samples from 102 patients were eligible for analysis. Twelve samples were polymerase chain reaction positive, and 14 samples were culture positive. The concordance of positive results when comparing these 2 methods was 71.4%. The most commonly found bacteria were Escherichia coli and Bacteroides fragilis. Of the 36 patients with complicated appendicitis, no bacteria were detected by either conventional culture or polymerase chain reaction in 21 (58%) of the patients. In patients with uncomplicated appendicitis, bacteria were demonstrated in 1 out of 66 (2%) patients.
CONCLUSION
This study suggests that polymerase chain reaction can be used to detect bacteria in the peritoneal fluid and has the potential to guide postoperative antibiotic treatment.
PubMed: 38862277
DOI: 10.1016/j.surg.2024.04.030