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The Journal of Clinical Investigation Apr 2024Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal... (Observational Study)
Observational Study Clinical Trial
Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, 2 patient cohorts were enrolled: patients with OvCa who underwent a diagnostic or cytoreductive surgery and nononcological patients, who underwent abdominal surgery for benign gynecological conditions and acted as the control group. Systematic extraction of PFD-sEVs from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage, and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEV proteomic profiles in high-grade serous ovarian carcinomas (HGSOCs) revealed 2 clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of PFD-sEV content provided a prognostic value with potential implications in HGSOC clinical management.
Topics: Humans; Female; Ovarian Neoplasms; Extracellular Vesicles; Ascitic Fluid; Middle Aged; Proteomics; Aged; Prospective Studies; Neoplasm Proteins; Adult
PubMed: 38564289
DOI: 10.1172/JCI176161 -
Journal of Clinical and Experimental... 2024We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive...
We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive for CD3 and CD5 and negative for CD56 and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization. CD4-positive cells and CD8-positive cells were mixed in almost equal numbers. He was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). The patient received one cycle of chemotherapy, resulting in severe sepsis. While undergoing treatment in the intensive care unit with an antimicrobial agent and prednisone, ascitic fluid appeared. Abdominal aspiration revealed neutrophil-predominant ascites and microbiological studies revealed Candida albicans. However, ascites did not improve when treated with micafungin for Candida peritonitis. Abdominal aspiration was re-performed, and atypical lymphoid cells that were positive for CD3 and CD56 were detected. EBV-DNA levels in whole blood were significantly elevated. Atypical lymphoid cells were positive for EBER by in situ hybridization and Southern blot analysis showed EBV terminal repeat monoclonal patterns. Bone marrow examination revealed the same atypical lymphoid cells. Therefore, the patient was diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL) with bone marrow involvement 3 months after the diagnosis of PTCL-NOS. Complications associated with PTCL-NOS and ENKTL are rare. PTCL-NOS, chemotherapy, sepsis, and prednisone might have led to immunodeficiency and reactivation of EBV, which might be one of the pathophysiologies for developing ENKTL. Our case indicates that measuring EBV-DNA in the blood is a simple and prompt examination to detect complications of EBV-associated lymphoma.
Topics: Male; Humans; Middle Aged; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoma, T-Cell, Peripheral; Prednisone; Lymphoma, Extranodal NK-T-Cell; Ascites; Killer Cells, Natural; DNA
PubMed: 38538319
DOI: 10.3960/jslrt.23049 -
Journal of Extracellular Vesicles Mar 2024High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC...
High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of 'core ascitic EV-associated proteins' but also defined their subset unique to HGSC ascites. Using single-cell RNA sequencing data, we mapped the origin of HGSC-specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non-malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type-specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics.
Topics: Humans; Female; Ascites; Tumor Microenvironment; Proteomics; Cystadenocarcinoma, Serous; Extracellular Vesicles; Ovarian Neoplasms
PubMed: 38490958
DOI: 10.1002/jev2.12420 -
Frontline Gastroenterology Mar 2024Using quality improvement techniques, we aimed to improve the rate of assessment and sampling of ascitic fluid for the purpose of diagnosing spontaneous bacterial...
OBJECTIVE
Using quality improvement techniques, we aimed to improve the rate of assessment and sampling of ascitic fluid for the purpose of diagnosing spontaneous bacterial peritonitis in patients with cirrhosis admitted to the hospitalist service of our institution.
DESIGN/METHODS
Based on stakeholder needs assessment, we implemented interventions targeting provider knowledge, procedure workflows and clinical decision support. We analysed key metrics during preintervention (September-December 2020), intervention roll-out (January-April 2021), postintervention (May-September 2021) and sustainability (September-December 2022) periods for admissions of patients with cirrhosis to our hospitalist service at Maine Medical Center, a 700-bed tertiary-care academic hospital in Portland, Maine, USA.
RESULTS
Among patients with cirrhosis admitted to our service, documentation of assessment for paracentesis increased from a preintervention baseline of 60.1% to 93.5% (p<0.005) postintervention. For patients with ascites potentially amenable to paracentesis, diagnostic paracentesis rate increased from 59.7% to 93% (p<0.005), with the rate of paracentesis within 24 hours increasing from 52.6% to 77.2% (p=0.01). These improvements persisted during our sustainability period. Complication rate was low (1.2%) across all study periods.
CONCLUSION
Our quality improvement project led to a sustained improvement in the identification of patients with cirrhosis needing diagnostic paracentesis and an increased procedure completion rate. This improvement strategy serves as a model for needed work toward closing a national performance gap for patients with cirrhosis.
PubMed: 38486668
DOI: 10.1136/flgastro-2023-102531 -
Journal of Community Hospital Internal... 2024Mycobacterium avium complex (MAC) infections can present as a variety of severe diseases. While it has a predilection for immunocompromised patients such as those with...
Mycobacterium avium complex (MAC) infections can present as a variety of severe diseases. While it has a predilection for immunocompromised patients such as those with Human immunodeficiency virus (HIV), it can also affect immunocompetent patients as well. One of the rare yet severe diseases that MAC infections can present is MAC peritonitis. Often hard to distinguish from other causes of peritonitis, high clinical suspicion should be maintained for those who are susceptible. Here we present an 85-year-old female with a past medical history of end-stage renal disease on peritoneal dialysis who presented with nausea and vomiting. She was found to have tenderness around her peritoneal dialysis site and was noted to have mild ascites. Her labs were significant for several electrolyte abnormalities, leukocytosis, and ascitic fluid obtained during a previous admission, and serology was positive for acid-fast bacilli. It was further revealed that the species was Mycobacterium avium complex. Initially, she started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE), subsequently antibiotics were changed to azithromycin, ethambutol, and rifampin after MAC identification in acid-fast bacilli culture. We aim to highlight this rare presentation of peritonitis secondary to MAC.
PubMed: 38482083
DOI: 10.55729/2000-9666.1300 -
International Journal of Molecular... Feb 2024Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics....
Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics. However, the rise of antibiotic resistance requires alternative therapeutic strategies. As recently shown, human amnion-derived mesenchymal stem cells (hA-MSCs) are able, in vitro, to promote bacterial clearance and modulate the immune and inflammatory response in SBP. Our results highlight the upregulation of FOXO1, CXCL5, CXCL6, CCL20, and MAPK13 in hA-MSCs as well as the promotion of bacterial clearance, prompting a shift in the immune response toward a Th17 lymphocyte phenotype after 72 h treatment. In this study, we used an in vitro SBP model and employed omics techniques (next-generation sequencing) to investigate the mechanisms by which hA-MSCs modify the crosstalk between immune cells in LPS-stimulated ascitic fluid. We also validated the data obtained via qRT-PCR, cytofluorimetric analysis, and Luminex assay. These findings provide further support to the hope of using hA-MSCs for the prevention and treatment of infective diseases, such as SBP, offering a viable alternative to antibiotic therapy.
Topics: Humans; Ascites; Lipopolysaccharides; Amnion; Liver Cirrhosis; Ascitic Fluid; Anti-Bacterial Agents; Peritonitis; Bacterial Infections; Forkhead Box Protein O1
PubMed: 38474048
DOI: 10.3390/ijms25052801 -
Cancers Mar 2024Ascites cytology is a cost-effective test for metastatic colorectal cancer (CRC) in the abdominal cavity. However, metastatic carcinoma of the peritoneum is difficult to...
Ascites cytology is a cost-effective test for metastatic colorectal cancer (CRC) in the abdominal cavity. However, metastatic carcinoma of the peritoneum is difficult to diagnose based on biopsy findings, and ascitic aspiration cytology has a low sensitivity and specificity and a high inter-observer variability. The aim of the present study was to apply artificial intelligence (AI) to classify benign and malignant cells in ascites cytology patch images of metastatic CRC using a deep convolutional neural network. Datasets were collected from The OPEN AI Dataset Project, a nationwide cytology dataset for AI research. The numbers of patch images used for training, validation, and testing were 56,560, 7068, and 6534, respectively. We evaluated 1041 patch images of benign and metastatic CRC in the ascitic fluid to compare the performance of pathologists and an AI algorithm, and to examine whether the diagnostic accuracy of pathologists improved with the assistance of AI. This AI method showed an accuracy, a sensitivity, and a specificity of 93.74%, 87.76%, and 99.75%, respectively, for the differential diagnosis of malignant and benign ascites. The diagnostic accuracy and sensitivity of the pathologist with the assistance of the proposed AI method increased from 86.8% to 90.5% and from 73.3% to 79.3%, respectively. The proposed deep learning method may assist pathologists with different levels of experience in diagnosing metastatic CRC cells of ascites.
PubMed: 38473421
DOI: 10.3390/cancers16051064 -
Journal of Nippon Medical School =... May 2024Endometriosis has several clinical features, including dysmenorrhea, infertility, and endometrioma (EMO). Although oxidative stress status is closely related to...
BACKGROUND
Endometriosis has several clinical features, including dysmenorrhea, infertility, and endometrioma (EMO). Although oxidative stress status is closely related to endometriosis, it is unclear how the balance between oxidative stress capacity and antioxidant capacity correlates with treatment of or factors that worsen endometriosis. In this study, we used peritoneal fluid from patients with EMO to investigate the role of oxidative stress capacity and antioxidant capacity.
MATERIALS AND METHODS
Participants with EMO (n = 30) and without EMO (uterine myoma, n = 13) were enrolled. All peritoneal fluid samples were collected at the beginning of surgery. We evaluated oxidative stress capacity and antioxidant capacity in peritoneal fluid samples by using the diacron-reactive oxygen metabolites (d-ROM) and biological antioxidant potential (BAP) tests, respectively. The d-ROM and BAP values and the d-ROM/BAP ratio were measured, and their correlations with the CA125 level, revised American Society for Reproductive Medicine (r-ASRM) score, and tumor size were analyzed.
RESULTS
The d-ROM/BAP ratio was significantly higher in patients with EMO than in those without EMO. In addition, the d-ROM/BAP ratio was positively correlated with CA125 level and r-ASRM scores in patients with EMO.
CONCLUSIONS
Oxidative stress is correlated with factors that worsen EMO. The d-ROM/BAP test may be useful for assessing disease status in patients with EMO.
Topics: Humans; Female; Endometriosis; Oxidative Stress; Antioxidants; Adult; Reactive Oxygen Species; Ascitic Fluid; CA-125 Antigen; Middle Aged
PubMed: 38432930
DOI: 10.1272/jnms.JNMS.2024_91-204 -
Cureus Jan 2024Introduction Limited studies are available for predicting mortality in patients with spontaneous bacterial peritonitis (SBP) based on ascitic fluid analysis. Recently, a...
Introduction Limited studies are available for predicting mortality in patients with spontaneous bacterial peritonitis (SBP) based on ascitic fluid analysis. Recently, a proposition has been made regarding the role of ascitic fluid lactate as a better prognostic indicator of mortality in cirrhotic patients with SBP. Therefore, we aimed to evaluate the utility of ascitic fluid lactate in predicting mortality in cirrhotic patients with SBP. Methods This was a prospective, observational study that was conducted in the Hepato-Gastroenterology Department of Sindh Institute of Urology and Transplantation (SIUT), Karachi from 1 January 2022 to 31 December 2022. All the patients having liver cirrhosis with ascites, aged between 18 and 65 years, and presenting with fever and/or abdominal pain were recruited in the study in the first six months (i.e., from 1 January 2022 to 30 June 2022) and were followed for six more months for the outcome. However, those patients on dialysis or those with hepatocellular carcinoma, any other malignancy as per a history of solid organ transplant, a history of HIV infection, or those underlying systemic sepsis or infections other than SBP were excluded from the study. The presence or absence of SBP was confirmed by doing the ascitic fluid analysis. Ascitic fluid lactate levels were also requested in each patient. Mortality was assessed at one, two, three, and six months, respectively. All the data were analyzed using SPSS version 23.0. The area under the receiver operating curve (AUROC) was obtained for ascitic fluid lactate for predicting mortality in SBP. At an optimal cutoff, the diagnostic accuracy of ascitic fluid lactate was obtained. Results The total number of cirrhotic patients included in the study was 123. The majority of the patients belong to Child Turcotte Pugh (CTP) class C (n = 88; 71%). Two third of the patients (65.8%; n = 81) had viral hepatitis i.e., hepatitis B, D, and/or C, as the cause of cirrhosis. Overall mortality was observed in 51(41.5%) patients. Ascitic fluid lactate was significantly raised in patients with SBP than in patients with non-SBP (p = 0.004). The AUROC of ascitic fluid lactate was highest at three months (AUROC = 0.88) followed by six months (AUROC = 0.84), two months (AUROC = 0.804), and one month (AUROC=0.773). At an optimal cut-off of more than or equal to 22.4 mg/dl, ascitic fluid lactate had a sensitivity of 84.9%, specificity of 85.7%, positive predictive value (PPV) of 97.3%, negative predictive value of 42.8% with diagnostic accuracy of 85% in predicting overall mortality in patients with SBP. On sub-analysis, the diagnostic accuracy of ascitic fluid lactate was highest at six months followed by at three, two, and one month, respectively. Conclusion Ascitic fluid lactate showed a good diagnostic utility in predicting the overall mortality in patients with SBP with the best diagnostic accuracy in predicting long-term (six months) mortality. However, further studies are required to validate our results.
PubMed: 38425592
DOI: 10.7759/cureus.53243 -
BMC Women's Health Feb 2024Endometriosis (EM) is a multifactorial disease that affects 10 - 15% of women of reproductive age. Additionally, 30-50% of women with EM suffer from infertility. The...
INTRODUCTION
Endometriosis (EM) is a multifactorial disease that affects 10 - 15% of women of reproductive age. Additionally, 30-50% of women with EM suffer from infertility. The mechanism of infertility caused by EM has not yet been consistently explained. In recent years, studies have shown a link between infertility associated with EM and changes in the reproductive tract microbiota.
METHODS
In this study, we involved 26 EM patients (8 cases of stage I-II and 18 cases of stage III-IV) and 31 control subjects who were tubal obstruction-related infertility (TORI). The samples from peritoneal fluid (PF) and uterine fluid (UF) were collected and sequenced by 16 S rRNA amplicon.
RESULTS
In the comparison of microbial diversity, we found no significant differences in the microbial diversity of PF and UF between patients with stage I-II EM and those with TORI. However, there was a significant difference in microbial diversity among patients with stage III-IV EM compared to the previous two groups. Lactobacillus decreased in PF of EM compared to the control group, while it increased in UF. In PF, the abundance of Pseudomonas, Enterococcus, Dubosiella and Klebsiella was significantly higher in patients with stage III-IV compared to TORI patients. And in UF, the main differences existed between stage I-II EM compared to the other two groups. The abundance of pontibacter, aquabacterium, Rikenellaceae and so on at the genus level was significantly enriched in the EM patients with stage I-II. In the analysis based on KEGG database, EM may affect the receptivity related pathways of the endometrium by influencing changes in the uterine microbiota.
CONCLUSION
Our results indicated that as EM progresses, the microorganisms in UF and PF keep changing. These changes in the microbiota, as well as the resulting alternations in gene functional classification, may play an important role in the infertility associated with EM.
Topics: Humans; Female; Endometriosis; Infertility, Female; Ascitic Fluid; Uterine Diseases; Endometrium
PubMed: 38424540
DOI: 10.1186/s12905-024-02985-5