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Cureus Dec 2023Background and aims Large-volume paracentesis (LVP) is a common practice for diuretic-refractory ascites in patients with cirrhosis. Spontaneous bacterial peritonitis...
Background and aims Large-volume paracentesis (LVP) is a common practice for diuretic-refractory ascites in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is reportedly low in asymptomatic patients presenting for elective outpatient LVP. The benefits and cost-effectiveness of routine testing for SBP in these patients are yet to be established. We aimed to investigate the incidence of SBP in outpatients who underwent elective LVP and the diagnostic yield of routine ascitic fluid testing, specifically fluid culture, and to assess the cost-effectiveness of these tests. Methods This is a retrospective study of adult patients undergoing outpatient LVP at Wollongong Hospital over three years. Symptomatic patients and patients with non-cirrhosis-related ascites were excluded. The ascitic fluid results were reviewed to determine if the polymorphonuclear (PMN) cell count was above 250 x 10/L and whether this was associated with positive fluid culture and clinical outcomes. The primary outcome was the incidence of SBP. The secondary outcome was the incidence of bacterascites. Results There were 26 patients with 122 elective ascitic taps. Two of 122 taps (1.6%) had ascitic PMN count above 250 x 10/L, indicating SBP. Four out of 122 taps (3.2%) had positive ascitic fluid cultures with a normal PMN count. All patients did not have significant clinical outcomes, did not receive antibiotic treatment, and remained asymptomatic over three years of follow-up. Conclusions Routine testing of ascitic fluid cell count and culture in asymptomatic patients with cirrhosis presenting for outpatient LVP yielded a low incidence of SBP and bacterascites, which were not clinically significant. Routine testing is costly and potentially exposes patients to antibiotics unnecessarily.
PubMed: 38077679
DOI: 10.7759/cureus.50191 -
International Journal of Molecular... Nov 2023A new method for the determination of cadherin 12 (CDH12)-an adhesive protein that has a significant impact on the development, growth, and movement of cancer cells-was...
A new method for the determination of cadherin 12 (CDH12)-an adhesive protein that has a significant impact on the development, growth, and movement of cancer cells-was developed and validated. The method is based on a biosensor using surface plasmon resonance imaging (SPRi) detection. A quartz crystal microbalance was used to analyze the characteristics of the formation of successive layers of the biosensor, from the linker monolayer to the final capture of CDH12 from solution. The association equilibrium constant (K = 1.66 × 10 dm mol) and the dissociation equilibrium constant (K = 7.52 × 10 mol dm) of the anti-CDH12 antibody-CDH12 protein complex were determined. The determined analytical parameters, namely the values determining the accuracy, precision, and repeatability of the method, do not exceed the permissible 20% deviations specified by the aforementioned institutions. The proposed method is also selective with respect to possible potential interferents, occurring in up to 100-fold excess concentration relative to the CDH12 concentration. The determined Limit of Quantification (LOQ = 4.92 pg mL) indicates the possibility of performing quantitative analysis in human plasma or peritoneal fluid without the need to concentrate the samples; however, particular attention should be paid to their storage conditions, as the analyte does not exhibit high stability. The Passing-Bablok regression model revealed good agreement between the reference method and the SPRi biosensor, with ρ values of 0.961 and 0.925.
Topics: Humans; Surface Plasmon Resonance; Ascitic Fluid; Biosensing Techniques; Cadherins
PubMed: 38069216
DOI: 10.3390/ijms242316894 -
Annals of Gastroenterology 2023Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cirrhotic cardiomyopathy. Few studies have addressed its clinical significance in cirrhosis....
BACKGROUND
Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cirrhotic cardiomyopathy. Few studies have addressed its clinical significance in cirrhosis. We assessed the association of LVDD with the factors affecting cirrhosis patients' severity, complications, and survival.
METHODS
A total of 203 cirrhosis patients were enrolled and underwent investigations, including 2-dimensional echocardiography with tissue Doppler imaging, and 139 patients with LVDD (cases) were compared with 64 patients without LVDD (controls). Logistic regression and Kaplan-Meier analysis were applied.
RESULTS
Mean age was 52.76±10 years. Among LVDD patients, 56% had grade-1, and 44% had grade-2 LVDD. Cirrhosis related to NASH had a more significant association with LVDD (P<0.001) than other etiologies. LVDD was significantly associated with a greater incidence of Child-Turcotte-Pugh (CTP) class C (P<0.001), higher model for end-stage liver disease scores (P=0.001), duration of cirrhosis >2 years since diagnosis (P=0.028), ascites (P<0.001), hepatic encephalopathy (P<0.010), hepatorenal syndrome (P<0.001), and a history of obesity (P=0.004). Multivariate analysis showed that higher CTP score, ascitic fluid protein and prolonged QTc interval were independently associated with LVDD (P=0.009; P=0.018; P=0.016, respectively). Kaplan-Meier survival analysis showed significantly poorer survival status in patients with higher grades of LVDD (P<0.001). The area under the receiver operating characteristic curve (0.78) was greatest for ascitic fluid protein in predicting LVDD, with a cutoff of >1 g/dL.
CONCLUSIONS
Higher CTP score, prolonged QTc, higher ascitic fluid protein levels, and poor survival are significantly associated with LVDD. Ascitic fluid protein >1 g/dL could be an indicator for evaluating LVDD.
PubMed: 38023969
DOI: 10.20524/aog.2023.0837 -
Molecular Oncology Jan 2024High-grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In...
High-grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites. This represents an early event in HGSOC development and is indicative of poor prognosis. In this study, based on tumorspheres isolated from ascitic liquid samples from HGSOC patients, ovarian cancer spheroid 3D cultures, and in vivo models, we describe a key signal for tumorsphere formation in HGSOC. We report that platelet-derived growth factor receptor beta (PDGFRβ) is essential for fibronectin-mediated cell clustering of ovarian cancer cells into tumorspheres. This effect is mediated by the kinase NUAK family SNF1-like kinase 1 (NUAK1) and blocked by PDGFRβ pharmacological or genetic inhibition. In the absence of PDGFRβ, ovarian cancer cells can be provided with fibronectin by cancer-associated fibroblasts to generate chimeric spheroids. This work provides new insights that uncover potential targets to prevent peritoneal dissemination, the main cause of advanced disease in HGSOC patients.
Topics: Humans; Female; Fibronectins; Ovarian Neoplasms; Ascites; Ascitic Fluid; Cancer-Associated Fibroblasts; Protein Kinases; Repressor Proteins
PubMed: 38010623
DOI: 10.1002/1878-0261.13556 -
Animals : An Open Access Journal From... Nov 2023In this study, strain C24 was isolated from cases of winter mortalities of hatchery-reared European seabass () broodstock in Türkiye. The first mortalities were...
In this study, strain C24 was isolated from cases of winter mortalities of hatchery-reared European seabass () broodstock in Türkiye. The first mortalities were reported in September 2016 and occurred annually in early autumn/late winter until the end of February 2019, when 15% of accumulated mortality was recorded. Diseased moribund fish exhibited general septicemic signs, including dermal ulcerations with hemorrhagic margins, distended abdomens, and hemorrhages below the pectorals, pelvic fins, and at the operculum. Postmortem findings showed congestion in several internal organs, hemorrhagic ascitic fluid, and congested prolapsed anal openings. The representative bacterial isolate strain C24 was characterized as Gram-negative, motile, nitrite-producing, and as vibrio static agent O/129-sensitive. The full-length 16S rRNA sequence (Accession No. ON778781) and gene sequence (Accession No. ON792326) of the C24 strain showed high similarity to strains. Moreover, the whole-genome average nucleotide identity (ANI) values (ANI > 97.7%) against four strains above the species demarcation limit unambiguously identified the C24 isolate as a member of this species. A preliminary virulence-gene analysis showed that the isolate C24 encoded at least three exotoxins, including two aerolysins and a thermolabile hemolysin. The experimental infection showed that the C24 isolate exhibited low to moderate virulence in experimentally infected European seabass juveniles. Interestingly, antimicrobial susceptibility testing revealed that the C24 isolate was susceptible to nalidixic acid, ciprofloxacin, and several other antibiotics but resistant to tilmicosin, kanamycin, streptomycin, and ampicillin. To our knowledge, this study is the first to report that could be considered an emerging bacterial pathogen in Türkiye, and it may threaten the international European seabass production.
PubMed: 38003197
DOI: 10.3390/ani13223580 -
Clinica Chimica Acta; International... Jan 2024Despite its limitations, the cytology of body fluids is widely used in diagnosing neoplastic cells. Flow cytometry detects and identifies individual cells, enabling the...
PURPOSE
Despite its limitations, the cytology of body fluids is widely used in diagnosing neoplastic cells. Flow cytometry detects and identifies individual cells, enabling the detection of circulating tumor cells and facilitating diagnosis. This study compared the diagnostic utility of flow cytometry and cytology for detecting cancer cells in peritoneal and pleural fluids.
METHODOLOGY
We used flow cytometry and cytology to examine 119 pleural and peritoneal effusions received for routine screening. Antibodies against clusters of differentiation 45 (CD45), 14 (CD14), and Epithelial cell adhesion molecule (EpCAM) were used to detect malignant cells. Based on combined clinical and diagnostic information, 37 fluid specimens were malignant, and 77 were benign.
RESULTS
Flow cytometry correctly identified 34 cancers, while cytology identified 26 cancers (sensitivity 91.89 % vs. 70.27, respectively). Both methods had equal specificity (98.7 %). At a cut-off of > 0.29 % EpCAM(+) cells to all cells in the samples, flow cytometry accurately detected cancer cells, achieving 89.2 % sensitivity, 90.9 % specificity, and an AUC of 0.959 (p < 0.001).
CONCLUSION
Flow cytometry improves the detection of epithelial cancer cells in peritoneal and pleural fluids compared to conventional cytology. Due to similar specificity and higher sensitivity, flow cytometry offers a promising alternative to cytology for patient screening.
Topics: Humans; Epithelial Cell Adhesion Molecule; Neoplastic Cells, Circulating; Flow Cytometry; Ascitic Fluid; Pleural Effusion, Malignant
PubMed: 37980974
DOI: 10.1016/j.cca.2023.117651 -
World Journal of Hepatology Oct 2023The lymphatic system is crucial in maintaining the body fluid homeostasis. A dysfunctional lymphatic system may contribute to the refractoriness of ascites and edema in...
BACKGROUND
The lymphatic system is crucial in maintaining the body fluid homeostasis. A dysfunctional lymphatic system may contribute to the refractoriness of ascites and edema in cirrhosis patients. Therefore, assessment of lymphatic dysfunction in cirrhosis patients with refractory ascites (RA) can be crucial as it would call for using different strategies for fluid mobilization.
AIM
To assessing the magnitude, spectrum, and clinical associations of lymphatic dysfunction in liver cirrhosis patients with RA.
METHODS
This observational study included 155 consecutive cirrhosis patients with RA. The presence of clinical signs of lymphedema, such as peau d'orange appearance and positive Stemmer sign, intestinal lymphangiectasia (IL) on duodenal biopsy seen as dilated vessels in the lamina propria with strong D2-40 immunohistochemistry, and chylous ascites were used to diagnose the overt lymphatic dysfunctions.
RESULTS
A total of 69 (44.5%) patients out of 155 had evidence of lymphatic dysfunction. Peripheral lymphedema, found in 52 (33.5%) patients, was the most common manifestation, followed by IL in 42 (27.0%) patients, and chylous ascites in 2 (1.9%) patients. Compared to patients without lymphedema, those with lymphedema had higher mean age, median model for end-stage liver disease scores, mean body mass index, mean ascitic fluid triglyceride levels, and proportion of patients with hypoproteinemia (serum total protein < 5 g/dL) and lymphocytopenia (< 15% of total leukocyte count). Patients with IL also had a higher prevalence of lymphocytopenia and hypoproteinemia (28.6% 9.1%, = 0.004). Seven (13%) patients with lymphedema had lower limb cellulitis compared to none in those without it. On multivariate regression analysis, factors independently associated with lymphatic dysfunction included obesity [odds ratio (OR): 4.2, 95% confidence intervals (95%CI): 1.1-15.2, = 0.027], lymphocytopenia [OR: 6.2, 95%CI: 2.9-13.2, < 0.001], and hypoproteinemia [OR: 3.7, 95%CI: 1.5-8.82, = 0.003].
CONCLUSION
Lymphatic dysfunction is common in cirrhosis patients with RA. Significant indicators of its presence include hypoproteinemia and lymphocytopenia, which are likely due to the loss of lymphatic fluid from the circulation. Future efforts to mobilize fluid in these patients should focus on methods to improve lymphatic drainage.
PubMed: 37970615
DOI: 10.4254/wjh.v15.i10.1140 -
International Journal of Molecular... Nov 2023Mesenchymal stem cells (MSCs) and their derivatives can be promising tools in oncology including ovarian cancer treatment. This study aimed to determine the effect of...
Mesenchymal stem cells (MSCs) and their derivatives can be promising tools in oncology including ovarian cancer treatment. This study aimed to determine the effect of HATMSC2-MVs (microvesicles derived from human immortalized mesenchymal stem cells of adipose tissue origin) on the fate and behavior of primary ovarian cancer cells. Human primary ovarian cancer (OvCa) cells were isolated from two sources: post-operative tissue of ovarian cancer and ascitic fluid. The phenotype of cells was characterized using flow cytometry, real-time RT-PCR, and immunofluorescence staining. The effect of HATMSC2-MVs on the biological activity of primary cells was analyzed in 2D (proliferation, migration, and cell survival) and 3D (cell survival) models. We demonstrated that HATMSC2-MVs internalized into primary ovarian cancer cells decrease the metabolic activity and induce the cancer cell death and are leading to decreased migratory activity of tumor cells. The results suggests that the anti-cancer effect of HATMSC2-MVs, with high probability, is contributed by the delivery of molecules that induce cell cycle arrest and apoptosis (p21, tumor suppressor p53, executor caspase 3) and proapoptotic regulators (bad, BIM, Fas, FasL, p27, TRAIL-R1, TRAIL-R2), and their presence has been confirmed by apoptotic protein antibody array. In this study, we demonstrate the ability to inhibit primary OvCa cells growth and apoptosis induction after exposure of OvCa cells on HATMSC2-MVs treatment; however, further studies are needed to clarify their anticancer activities.
Topics: Humans; Female; Mesenchymal Stem Cells; Apoptosis; Adipose Tissue; Ovarian Neoplasms; Cell-Derived Microparticles
PubMed: 37958844
DOI: 10.3390/ijms242115862 -
Insights Into Imaging Nov 2023To assess the frequency of appearance of various signs (isolated and grouped) in emergency imaging tests in patients with anisakiasis, according to the location of...
BACKGROUND
To assess the frequency of appearance of various signs (isolated and grouped) in emergency imaging tests in patients with anisakiasis, according to the location of gastrointestinal tract involvement.
METHODS
Retrospective review by two experienced radiologists of emergency ultrasounds and CTs performed on patients admitted in the Emergency Department of our hospital with later confirmed anisakiasis (2010-2021), assessing the presence of signs suggesting anisakiasis. Calculation of the frequency of appearance according to the gastric or intestinal location, as well as the most common grouped signs.
RESULTS
Out of 231 total patients with anisakiasis, imaging studies were performed in 144: abdominopelvic ultrasound in 43 cases and CT in 111 (both techniques in 31). In cases with gastric occurrence (34), in CT the wall stratification (100%), wall thickening (97%), fat stranding (91%) and ascitic fluid (82%) were predominant. In the intestinal cases (105), in CT (95) the wall thickening (100%), fat stranding (92%) and mesenteric vessel engorgement (83%) were usual; in ultrasound (40), ascitic fluid and wall thickening (70% in both cases) were frequently observed. The frequency of grouped appearance of the mentioned signs was 82% in gastric cases, 80% in intestinal cases and 50% in ultrasounds. Multisegment involvement in CT reached 28% (gastric + intestinal) and 11% (only intestinal) of cases.
CONCLUSIONS
The most frequent CT findings in patients with gastric anisakiasis are wall stratification and thickening, fat stranding and ascitic fluid. In the intestinal cases, wall thickening, fat oedema and vessel engorgement are the most often observed findings.
CRITICAL RELEVANCE STATEMENT
The presence of different radiological signs makes it advisable to include anisakiasis in the differential diagnosis of acute abdomen. Intestinal and multifocal involvement rates are greater than previously reported.
KEY POINTS
• In gastric anisakiasis, CT frequently shows wall stratification and thickening, fat stranding and ascitic fluid. • In intestinal anisakiasis, CT often presents wall thickening, fat stranding and vessel engorgement. • In intestinal anisakiasis, ultrasounds most frequently show ascitic fluid and wall thickening.
PubMed: 37953399
DOI: 10.1186/s13244-023-01511-9 -
Molecular Cancer Nov 2023Knowing the homologous recombination deficiency (HRD) status in advanced epithelial ovarian cancer (EOC) is vital for patient management. HRD is determined by...
BACKGROUND
Knowing the homologous recombination deficiency (HRD) status in advanced epithelial ovarian cancer (EOC) is vital for patient management. HRD is determined by BRCA1/BRCA2 pathogenic variants or genomic instability. However, tumor DNA analysis is inconclusive in 15-19% of cases. Peritoneal fluid, available in > 95% of advanced EOC cases, could serve as an alternative source of cell-free tumor DNA (cftDNA) for HRD testing. Limited data show the feasibility of cancer panel gene testing on ascites cfDNA but no study, to date, has investigated HRD testing.
METHODS
We collected ascites/peritoneal washings from 53 EOC patients (19 from retrospective cohort and 34 from prospective cohort) and performed a Cancer Gene Panel (CGP) using NGS for TP53/HR genes and shallow Whole Genome Sequencing (sWGS) for genomic instability on cfDNA.
RESULTS
cfDNA was detectable in 49 out of 53 patients (92.5%), including those with limited peritoneal fluid. Median cfDNA was 3700 ng/ml, with a turnaround time of 21 days. TP53 pathogenic variants were detected in 86% (42/49) of patients, all with HGSOC. BRCA1 and BRCA2 pathogenic variants were found in 14% (7/49) and 10% (5/49) of cases, respectively. Peritoneal cftDNA showed high sensitivity (97%), specificity (83%), and concordance (95%) with tumor-based TP53 variant detection. NGS CGP on cftDNA identified BRCA2 pathogenic variants in one case where tumor-based testing failed. sWGS on cftDNA provided informative results even when tumor-based genomic instability testing failed.
CONCLUSION
Profiling cftDNA from peritoneal fluid is feasible, providing a significant amount of tumor DNA. This fast and reliable approach enables HRD testing, including BRCA1/2 mutations and genomic instability assessment. HRD testing on cfDNA from peritoneal fluid should be offered to all primary laparoscopy patients.
Topics: Female; Humans; BRCA1 Protein; BRCA2 Protein; Mutation; Ovarian Neoplasms; Circulating Tumor DNA; Homologous Recombination; Ascitic Fluid; Ascites; Prospective Studies; Retrospective Studies; Carcinoma, Ovarian Epithelial; Genomic Instability
PubMed: 37932736
DOI: 10.1186/s12943-023-01864-1