Overexpression of Fut 2, 4, and 8, and nuclear localization of Fut 4 in ovarian cancer cell lines induced by ascitic fluids from epithelial ovarian cancer patients.

Fucosyltransferases (Fut) regulate the fucosylation process associated with tumorogenesis in different cancer types. Ascitic fluid (AF) from patients diagnosed with advanced stage of epithelial ovarian cancer (EOC) is considered as a dynamic tumor microenvironment associated with poor prognosis. Previous studies from our laboratory showed increased fucosylation in SKOV-3 and OVCAR-3, cancer-derived cell lines, when these cells were incubated with AFs derived from patients diagnosed with EOC. In the present work we studied three fucosyltransferases (Fut 2, Fut 4, and Fut 8) in SKOV-3, OVCAR-3 and CAOV-3 cell lines in combination with five different AFs from patients diagnosed with this disease, confirming that all tested AFs increased fucosylation. Then, we demonstrate that mRNAs of these three enzymes were overexpressed in the three cell lines under treatment with AFs. SKOV-3 showed the higher overexpression of Fut 2, Fut 4, and Fut 8 in comparison with the control condition. We further confirmed, in the SKOV-3 cell line, by endpoint PCR, WB, and confocal microscopy, that the three enzymes were overexpressed, being Fut 4 the most overexpressed enzyme compared to Fut 2 and Fut 8. These enzymes were concentrated in vesicular structures with a homogeneous distribution pattern throughout the cytoplasm. Moreover, we found that among the three enzymes, only Fut 4 was located inside the nuclei. The nuclear location of Fut 4 was confirmed for the three cell lines. These results allow to propose Fut 2, Fut 4, and Fut 8 as potential targets for EOC treatment or as diagnostic tools for this disease.

Differential diagnosis of ascites: etiologies, ascitic fluid analysis, diagnostic algorithm.

Ascites is the pathological accumulation of fluid within the peritoneal cavity. It often occurs as results of liver cirrhosis, malignant neoplasia, tuberculous infection, cardiac insufficiency, renal diseases, etc. Determining the etiology is an essential step in the management of patients with new-onset ascites. Abdominal paracentesis with appropriate ascitic fluid analysis is probably the most cost-effective method of determining the cause of ascites. We performed a literature search of PubMed and identified articles published in the field of ascites, to evaluate diagnostic values of various parameters in defining the etiologies of ascites and then provides diagnostic algorithm for patients with new-onset ascites. In patients with ascites, the constituent ratio of underlying etiology varies between developed and developing countries. It is a challenge to define the etiologies of ascites in developing countries. Routine ascitic fluid analysis should include the serum ascites albumin gradient (SAAG), total protein concentration, cell count and differential. Optional ascitic fluid analysis includes cholesterol, fluid culture, cytology, tumor markers, lactate dehydrogenase, adenosine deaminase (ADA), triglyceride, amylase, glucose, brain natriuretic peptide (BNP), etc. Our review evaluated diagnostic values of the above parameters in defining the etiologies of ascites. Diagnostic algorithm established in this review would provide a practical and convenient diagnostic strategy for clinicians in diagnosing patients with new-onset ascites.

Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation.

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.

Potential drug repurposing of ruxolitinib to inhibit the JAK/STAT pathway for the treatment of patients with epithelial ovarian cancer.

AIM: This review aimed to describe the potential for therapeutic targeting of the JAK/STAT signaling pathway by repurposing the clinically-approved JAK inhibitor ruxolitinib in the patients with epithelial ovarian cancer (OC) setting. METHODS: We reviewed publications that focus on the inhibition of the JAK/STAT pathway in hematological and solid malignancies including OC. RESULTS: Preclinical studies showed that ruxolitinib effectively reduces OC cell viability and metastasis and enhances the anti-tumor activity of chemotherapy drugs. There are a number of recent clinical trials exploring the role of JAK/STAT inhibition in solid cancers including OC. Early results have not adequately supported efficacy in solid tumors. However, there are preclinical data and clinical studies supporting the use of ruxolitinib in combination with both chemotherapy and other targeted drugs in OC setting. CONCLUSION: Inflammatory conditions and persistent activation of the JAK/STAT pathway are associated with tumourigenesis and chemoresistance, and therapeutic blockade of this pathway shows promising results. For women with OC, clinical investigation exploring the role of ruxolitinib in combination with chemotherapy agents or other targeted therapeutics is warranted.

Ascitic Fluid Calprotectin And Ratio Of Calprotectin To Total Protein In Spontaneous Bacterial Peritonitis.

Objectives: To evaluate the diagnostic and prognostic role of ascitic fluid calprotectin and its ratio to total protein in spontaneous bacterial peritonitis cases. Method: The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2019 to December 2020, and comprised cirrhotic patients of either gender with ascites. Diagnostic abdominal paracentesis was performed for all patients and ascetic fluid calprotectin was measured. Patients were followed for development of spontaneous bacterial peritonitis or mortality. Data was analysed using SPSS 20. RESULTS: Of the 90 patients, 61(67.7%) were males and 29(32.2%) were females. There were 67(74.4%) patients with spontaneous bacterial peritonitis; 48(71.6%) males and 19(28.3%) females with mean age 60.42±8.3 years. The remaining 23(25.5%) did not have spontaneous bacterial peritonitis; 13(56.5%) males and 10(43.4%) females with mean age 59.7±7.4 years. The patients had significantly higher calprotectin, and calprotectin/total protein ratio (p<0.05). Logistic regression identified ascitic fluid calprotectin as a significant predictor of mortality (p=0.05). The non-survivors had significantly higher ascitic fluid calprotectin and calprotectin/total protein ratio compared to the survivors (p<0.05). CONCLUSIONS: Ascites calprotectin level and itsratio to total protein wasfound to be accurate diagnostic and predictive biomarkers for spontaneous bacterial peritonitis.

Exploring the clinical value of tumor microenvironment in platinum-resistant ovarian cancer.

Platinum resistance in epithelial ovarian cancer (OvCa) is rising at an alarming rate, with recurrence of chemo-resistant high grade serous OvCa (HGSC) in roughly 75 % of all patients. Additionally, HGSC has an abysmal five-year survival rate, standing at 39 % and 17 % for FIGO stages III and IV, respectively. Herein we review the crucial cellular interactions between HGSC cells and the cellular and non-cellular components of the unique peritoneal tumor microenvironment (TME). We highlight the role of the extracellular matrix (ECM), ascitic fluid as well as the mesothelial cells, tumor associated macrophages, neutrophils, adipocytes and fibroblasts in platinum-resistance. Moreover, we underscore the importance of other immune-cell players in conferring resistance, including natural killer cells, myeloid-derived suppressive cells (MDSCs) and T-regulatory cells. We show the clinical relevance of the key platinum-resistant markers and their correlation with the major pathways perturbed in OvCa. In parallel, we discuss the effect of immunotherapies in re-sensitizing platinum-resistant patients to platinum-based drugs. Through detailed analysis of platinum-resistance in HGSC, we hope to advance the development of more effective therapy options for this aggressive disease.

Distribution evaluation of tacrolimus in the ascitic fluid of liver transplant recipients with liver cirrhosis by a sensitive ultra-performance liquid chromatography-tandem mass spectrometry method.

Tacrolimus has a narrow therapeutic index and large individual differences in pharmacokinetics. The distribution of tacrolimus in ascitic fluid and its influence on whole-blood tacrolimus were unclear. In this study, a sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was established and validated for the quantification of tacrolimus in the ascitic fluid of liver transplant recipients. Chromatographic separation was achieved on an Agilent ZORBAX Eclipse Plus Phenyl-Hexyl column (2.1 × 100 mm, 3.5 µm). Mass spectrometry was performed in multiple reaction monitoring conditions of transitions m/z 821.4→768.5 for tacrolimus. The concentrations of tacrolimus in the ascitic fluid range from 0.2 to 3.0 ng/mL, accounting for 1.19-31.87% of whole-blood tacrolimus concentrations. A linear mixed model showed a statistically significant positive correlation between the steady-state trough blood concentration of tacrolimus and the corresponding amount of tacrolimus excreted in the ascitic fluid for 24 consecutive hours, especially after normalization by daily dose per unit body weight. These data suggested that the distribution of tacrolimus in the ascitic fluid has great individual differences. The whole-blood tacrolimus concentration, dose per unit body weight, and other confounding factors may contribute to the excretion of tacrolimus in ascitic fluid, but the influence of tacrolimus excretion in drained ascitic fluid on the whole-blood tacrolimus concentration is negligible.

Human Amnion-Derived Mesenchymal Stromal Cells: A New Potential Treatment for Carbapenem-Resistant Enterobacterales in Decompensated Cirrhosis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe and often fatal infection in patients with decompensated cirrhosis and ascites. The only cure for SBP is antibiotic therapy, but the emerging problem of bacterial resistance requires novel therapeutic strategies. Human amniotic mesenchymal stromal cells (hA-MSCs) possess immunomodulatory and anti-inflammatory properties that can be harnessed as a therapy in such a context. METHODS: An in vitro applications of hA-MSCs in ascitic fluid (AF) of cirrhotic patients, subsequently infected with carbapenem-resistant Enterobacterales, was performed. We evaluated the effects of hA-MSCs on bacterial load, innate immunity factors, and macrophage phenotypic expression. RESULTS: hA-MSCs added to AF significantly reduce the proliferation of both bacterial strains at 24 h and diversely affect M1 and M2 polarization, C3a complement protein, and ficolin 3 concentrations during the course of infection, in a bacterial strain-dependent fashion. CONCLUSION: This study shows the potential usefulness of hA-MSC in treating ascites infected with carbapenem-resistant bacteria and lays the foundation to further investigate antibacterial and anti-inflammatory roles of hA-MSC in in vivo models.

Ascitic Fluid Cytokines in Chronic Liver Disease: A Possible Prognostic Tool.

INTRODUCTION: Malignant ascites results from imbalance between protein in the peritoneal cavity and absorption of fluids via the lymphatic system. More than 20 interleukins (ILs) are known to play an important role in the protection against tumors. MATERIALS AND METHODS: Ascitic fluid IL-1B, IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ levels were assessed in 45 patients with liver cirrhosis and ascites as judged by histopathological and ultrasonographic findings. They were divided into 2 groups according to presence of hepatic focal lesions. Ten patients with focal hepatic lesions were randomly selected and subjected to analysis of serum levels of IL-2 and IL-10. RESULTS: Ascitic fluid IL-4, IL-6 and IL-10 levels were found to be significantly higher in patients with hepatocellular carcinoma (HCC) than patients with cirrhosis. TNF-α, and IFN-γ were also found to be higher in HCC than patients with cirrhosis but with no significance. On the other hand, there was no significant difference in levels of IL-1B and IL-2 between the 2 groups. Ascitic fluid IL-2 and IL-10 levels were found to be higher in ascitic fluid than in serum of the same patients. CONCLUSION: Ascitic fluid levels of IL-4, IL-6 and IL-10 are higher in HCC patients than patients with cirrhosis alone. Levels of ascitic fluid IL-2 and IL-10 proved to be a better prognostic tool than their levels in sera of the same patients. To conclude, patients with cirrhosis may be subjected to scheduled examination of ascitic fluid cytokines to predict transformation into HCC.

Efficacy and safety of tolvaptan in patients with malignant ascites: a phase 2, multicenter, open-label, dose-escalation study.

OBJECTIVE: This phase 2 study examined the efficacy and safety of tolvaptan, an aquaretic drug, in the treatment of ascites associated with cancer. METHODS: In the dose-escalation phase, oral tolvaptan was initiated at a dose of 3.75 mg/day, and the dose was increased daily to 7.5, 15 and 30 mg/day. Dose escalation was terminated once the increase from baseline in the daily urine volume reached 500 ml, at which point the patient proceeded to the maintenance phase of 5-7 days. Improvement of ascites was determined primarily by reduction in body weight and ascitic fluid volume. RESULTS: The mean change from baseline in body weight was maintained below 0 kg throughout the study. The mean change (±standard deviation) from baseline in ascitic fluid volume at the end of treatment (EOT) was 237.45 ± 868.14 ml in 33 evaluable patients. Although an increase from baseline in ascitic fluid volume at the EOT was observed in 23 of 33 patients (maximum: 1589.3 ml, minimum: 3.83 ml), a reduction in ascitic fluid volume was observed in the remaining 10 patients (maximum: -2304.3 ml, minimum: -27.5 ml). The common treatment-emergent adverse events included vomiting (5 of 43 patients, 11.6%), abdominal distension, constipation, thirst, blood osmolarity increased and renal impairment (3 of 43 patients, 7.0% each). CONCLUSIONS: Tolvaptan seemed to have no definitive effect on reducing ascites; however, it might be effective in at least some cancer patients. No new safety concerns were identified at doses of 3.75-30 mg/day.

Frequency and prediction of deep uterine involvement in advanced high-grade epithelial ovarian cancer: is uterine preservation an option?

INTRODUCTION: Hysterectomy is traditionally part of the surgical treatment for advanced high-grade epithelial ovarian carcinomas, although the incidence of uterine involvement has not been fully investigated. Some young patients with advanced high-grade epithelial ovarian carcinomas want uterine preservation. We aimed to determine the frequency of non-serosal (deep) uterine involvement in patients with high-grade epithelial ovarian carcinomas and to establish predictive factors for such involvement. METHODS: A retrospective cohort study was performed of 366 consecutive patients with advanced high-grade epithelial ovarian carcinomas who had surgery between January 2012 and December 2019. Data collected included demographic and clinical details, and surgical and pathological reports to determine macroscopic and microscopic deep uterine involvement. The characteristics of the patients with and without deep uterine involvement were compared and univariate and multivariate Cox proportional hazard models were used to assess correlations and determine risk factors. RESULTS: A total of 311 patients were included in the final analysis. The mean age was 62±11.6 years, with 32 (10.3%) being younger than 45. Most (92.3%) had serous carcinoma. Uterine involvement, excluding superficial (serosa-only), was present microscopically in 194 patients (62.4%) but was detected macroscopically at surgery in only 166 patients. Deep involvement was missed at surgery in 28 patients (14.4%), including parametrial involvement (n=18), parametria plus cervix (n=2), cervical involvement (n=3), endometrium (n=3), and myometrium (n=2). Multivariate analysis identified factors associated with deep uterine involvement including residual disease at surgery (HR 2.43, 95% CI 1.13 to 4.48; p=0.004) and CA125 >1000 U (HR 1.8, 95% CI 1.09 to 2.94; p=0.02). CONCLUSIONS: The incidence of deep uterine involvement in high-grade epithelial ovarian carcinomas is high. It can be diagnosed in most but not all cases on gross examination at surgery and is associated with residual disease and CA125 >1000 U. Patients who desire uterine preservation should be advised on an individual basis, given these factors and the operative findings.

Efficacy of ascitic fluid cell block for diagnosing primary ovarian, peritoneal, and tubal cancer in patients with peritoneal carcinomatosis with ascites.

OBJECTIVE: To compare the efficacy of ascitic fluid cell block (ACB) with that of core needle biopsy (CNB) or the CA125/CEA ratio in diagnosing primary tubo-ovarian cancer in female patients with peritoneal carcinomatosis (PC) with ascites. METHODS: This retrospective study examined female patients with PC with ascites who had available results for ACB, peritoneal tumor CNB, and the CA125/CEA ratio. Several measures of the accuracy of ACB and the CA125/CEA ratio were calculated and compared, with CNB as the reference standard. RESULTS: Of 81 patients with available results, 57 were clinically diagnosed with primary tubo-ovarian cancer. Overall, 52, 47, and 64 patients were diagnosed via CNB, ACB, and CA125/CEA ratio > 25, respectively. CNB and ACB identified the cancer origin in 91.4% and 82.7% cases, respectively. The concordance ratio of the immunohistochemical findings between ACB and CNB was 93.6%. Two patients with inconclusive CNB results were diagnosed with primary tubo-ovarian cancer via ACB. The sensitivity, specificity, positive predictive value, negative predictive value, and positive likelihood ratio were 86.5%, 93.1%, 95.7%, 79.4%, and 12.5, respectively, for ACB and 94.2%, 48.3%, 76.6%, 82.4%, and 1.82, respectively, for CA125/CEA ratio > 25. CONCLUSIONS: ACB is not inferior to CNB in diagnosing primary tubo-ovarian cancer; the two methods complement each other. ACB can substitute CNB in diagnosing primary tubo-ovarian cancer in selected PC patients. ACB is superior to a CA125/CEA ratio of >25 in diagnosing primary tubo-ovarian cancer. ACB is effective, reliable, and convenient for diagnosing primary tubo-ovarian cancer in PC patients with ascites.

Is ascites CEA a risk factor for peritoneal carcinomatosis in colorectal cancer?: a long-term follow-up study.

PURPOSE: Our previous study reported that carcinoembryonic antigen (CEA) levels in peritoneal fluid were significantly correlated with the prevalence of peritoneal carcinomatosis (PC) in colorectal cancer (CRC). The purpose of this study was a long-term follow up of the author's previous study, as well as the identification of correlations with the known risk factors of PC and the comparison of the predictive power of PC in CRC. METHODS: A total of 495 patients without PC who underwent CRC operations at St. Mary's Hospital, The Catholic University of Korea, from January 2006 to November 2014 were included in this study. Tumor markers of peritoneal fluid sampled at the beginning of each operation were prospectively analyzed and compared with the known risk factors for PC in CRC. RESULTS: Multivariate analysis of PC revealed that T4 cancer (OR 5.143, 95% CI 1.400-18.897, p = 0.014), T3 mucinous cancer (OR 17.480, 95% CI 1.577-193.714, p = 0.020), obstructed tumors (OR 6.030, 95% CI 1.627-22.343, p = 0.007), and peritoneal fluid CEA above 5 ng/dl (OR 4.073, 95% CI 1.315-12.615, p = 0.015) were significant risk factors. T4 cancer, obstructed tumors, and peritoneal fluid CEA above 5 ng/dl showed correlations with cancer-free survival. Generally, higher CEA levels in peritoneal fluid were correlated with previously known risk factors for PC in CRC. CONCLUSION: Peritoneal fluid CEA has predictive value for PC and prognostic value in CRC. Therefore, we recommend routinely performing ascites CEA analysis in colorectal cancer surgery.

Ascitic fluid total protein, a useful marker in non-portal hypertensive ascites.

BACKGROUND AND AIMS: Diagnostic performance of ascitic fluid total protein (AFTP) concentration remained unsettled. Our aim was to determine diagnostic value of AFTP in differential diagnosis of causes of ascites. METHODS: Seven hundred four consecutive patients with new-onset ascites were prospectively enrolled in this study. RESULTS: In the training cohort, diagnostic performance of quantitative AFTP assay was superior to that of Rivalta test in differential diagnosis of ascites. At the predetermined cut-off value of 25 g/L, quantitative AFTP assay was more useful in the differentiation of non-portal hypertensive ascites from portal hypertensive ascites compared with the exudate-transudate classification, area under curve of receiver operating characteristic curve was 0.958. Quantitative AFTP assay was superior to serum-ascites albumin gradient in the detection of non-portal hypertensive ascites, especially malignant ascites and tuberculous peritonitis. In mixed ascites, AFTP was useful in identifying peritoneal lesions. CONCLUSIONS: Ascitic fluid total protein is a useful marker in non-portal hypertensive ascites; thus, it should be determined in diagnostic work-up of the patients with ascites.

EV-associated miRNAs from peritoneal lavage as potential diagnostic biomarkers in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality worldwide. Current systematic methods for diagnosing have inherent limitations so development of a minimally-invasive diagnosis, based on the identification of sensitive biomarkers in liquid biopsies could therefore facilitate screening among population at risk. METHODS: In this study, we aim to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the peritoneal lavage as a source of potential miRNA diagnostic biomarkers. We isolated EVs by ultracentrifugation from 25 ascitic fluids and 25 peritoneal lavages from non-cancer and CRC patients, respectively. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 371 miRNAs. RESULTS: 210 miRNAs were significantly dysregulated (adjusted p value < 0.05 and abs(logFC) ≥ 1). The top-10 miRNAs, which had the AUC value higher than 0.95, were miRNA-199b-5p, miRNA-150-5p, miRNA-29c-5p, miRNA-218-5p, miRNA-99a-3p, miRNA-383-5p, miRNA-199a-3p, miRNA-193a-5p, miRNA-10b-5p and miRNA-181c-5p. CONCLUSIONS: This finding opens the avenue to the use of EV-associated miRNA of peritoneal lavages as an untapped source of biomarkers for CRC.

Novel association of Streptococcus gallolyticus subspecies pasteurianus and hepatocelluar carcinoma: opening new frontiers.

BACKGROUND: Streptococcus gallolyticus subsp. gallolyticus bacteremia is associated with colorectal malignancies. There is limited data regarding the association of Streptococcus gallolyticus subsp. pasteurianus with malignancies. We aimed to study the pattern of isolation of Streptococcus gallolyticus and analysis of risk factors in patients with hepatobiliary diseases. We also planned to evaluate its association with hepatocellular malignancy. METHODS: We analyzed clinical and laboratory data of 68 cases of Streptococcus gallolyticus infections (77 isolates) from January 2013 to December 2017. These included blood (58), ascitic fluid (15), bile (2) and pleural fluid (2). We analyzed the risk factors in patients developing malignancy with Streptococcus gallolyticus infections. RESULTS: Amongst the 68 patients studied, eight (11.76%) had confirmed malignancies, hepatocellular carcinoma (HCC) (5), rectal adenocarcinoma (1), pancreatic carcinoma (1) and uterine tumors (1). Simultaneous isolation of S. gallolyticus subsp. pasteurianus from blood and ascitic fluid in eight patients (11.8%, p = .01) was significantly associated with the occurrence of HCC. Streptococcus gallolyticus infection with HCC was associated with younger age (median 55 years), lymphocytosis and elevated gamma-glutamyl transferase (GGT). CONCLUSIONS: This study provides a novel insight into the association of Streptococcus gallolyticus subspecies pasteurianus with HCC. The isolation of the organism from blood and ascitic fluid should prompt the clinicians to search for evidence of HCC actively.

Low ascitic fluid total protein levels is not associated to the development of spontaneous bacterial peritonitis in a cohort of 274 patients with cirrhosis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a complication to decompensated cirrhosis. Fluoroquinolones may prevent SBP. However, predictive markers for SBP are wanted. Guidelines suggest that patients with ascitic fluid protein below 15 g/l receive fluoroquinolones to prevent SBP. This study aimed to assess the clinical utility of low ascitic fluid protein in predicting SBP in patients with cirrhosis and ascites. METHODS: A total of 274 patients with cirrhosis and ascites underwent paracentesis between January 2010 and June 2015. Patients were followed until two years, development of SBP, initiation of ciprofloxacin, death or liver transplantation. Data were compared between groups of patients with 'high' or 'low' ascitic protein. RESULTS: SBP developed in 31 patients (11.3%). No difference in mean ascitic fluid protein levels were found (SBP, mean: 8.5 g/l and no SBP 8.2 g/l, p = .825). SBP developed at equal rates in patients with 'high' or 'low' ascitic protein (10.8% (≤15 g/l) and 14.0% (>15 g/l), p = .599). The same trend was observed when adjusting the threshold below 10 g/l (11.9% (≤10 g/l) and 10.2% (>10 g/l), p = .697). CONCLUSIONS: Low ascitic fluid protein does not predict SBP in patients with cirrhosis and ascites. Better markers are needed.

Combination of PCT, sNFI and dCHC for the diagnosis of ascites infection in cirrhotic patients.

BACKGROUND: It is difficult to diagnose ascites infection early in cirrhotic patients. The present study was to create and evaluate a new bioscore combined with PCT, sNFI and dCHC in the diagnosis of ascites infection in cirrhotic patients. METHODS: Two hundred and fifty-nine consecutive patients were enrolled; of which 51 patients were culture-positive spontaneous bacterial peritonitis (culture-positive SBP) and 58 patients were culture-negative SBP. The efficacy of procalcitonin(PCT), c-reactive protein (CRP), white blood cell (WBC), mean fluorescence intensity of mature neutrophils(sNFI) and difference in hemoglobin concentration between newly formed and mature red blood cells(dCHC) for diagnosing ascites infection was examined. These parameters were used to create a scoring system. The scoring system was analyzed by logistic regression analysis to determine which parameters were statistically different between ascites infection and non-ascites infection patients. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic ability of bioscore for ascites infection. RESULTS: In ROC analysis, the area under the curves (AUC) for PCT was 0.852 (95% CI 0.803-0.921, P < 0.001), dCHC 0.837 (95% CI 0.773-0.923, P < 0.001), CRP 0.669 (95% CI 0.610-0.732, P = 0.0624), sNFI 0.838 (95% CI 0.777-0.903, P < 0.001), and WBC 0.624 (95% CI 0.500-0.722, P = 0.0881). Multivariate analysis revealed PCT, dCHC and sNFI to be statistically significant. The combination of these three parameters in the bioscore had an AUC of 0.937 (95% CI 0.901-0.994, P < 0.001). A bioscore of ≥3.40 was considered to be statistically significant in making a positive diagnosis of ascites infection. In different groups of ascites infection, bioscore also shown a high diagnostic value of AUC was 0.947(95% CI 0.882-0.988, P < 0.001) and 0.929 (95% CI 0.869-0.974, P < 0.001) for culture-positive SBP and culture-negative SBP group respectively. CONCLUSION: The composite markers of combining PCT, dCHC and sNFI could be a valuable diagnostic score to early diagnose ascites infection in patients with cirrhosis.

Ascites in an uncorrected tetralogy of Fallot with pulmonary valve absence in an adult patient.

This is a case of a 37-year-old woman with uncorrected tetralogy of Fallot with the absence of pulmonary valve and history of heart murmur in childhood who did not have a medical approach. At 29 years of age she started with dyspnoea that in the last 7 months progressed to be of small effort and also referred increase of the abdominal perimeter.

Characterization of ascites in cardiac cirrhosis: the value of ascitic fluid protein to screen for concurrent cardiac cirrhosis.

Abstracts Objectives: Cardiogenic ascites has been well described regarding its pathophysiology and fluid characteristics in prior literatures. However, ascites in patients with cardiac cirrhosis has not been characterized as a separate entity despite its unique pathophysiology and clinical aspects. This study aims to describe the fluid profile of ascites of cardiac cirrhosis and explore the utility of ascitic fluid protein (AFP) to predict concurrent cardiac cirrhosis. METHODS AND MATERIALS: We retrospectively selected and reviewed samples from the patients with cardiogenic ascites with and without concurrent cardiac cirrhosis. Epidemiologic characters, serum laboratory values, and fluid characteristics were directly compared between the groups. RESULTS: We analyzed 20 samples of ascitic fluid from the patients of cardiac cirrhosis and compared with 48 samples of non-cirrhotic cardiac ascites. The AFP was significantly lower in patients with cardiac cirrhosis (3.66g/dl) as compared to non-cirrhotic patients (4.31g/dl, p < .01); while there was no difference in serum-ascites albumin gradient (1.48g/dl vs. 1.47g/dl, p = .95). AFP equal to or less than 4.3g/dl predicted cirrhosis with a sensitivity of 95% and negative likelihood ratio of 0.10; the corresponding ROC curve of AFP has an AUC of 0.777, higher than AUC of other noninvasive prediction models. CONCLUSIONS: We presented the first fluid characterization of ascites in patients with cardiac cirrhosis. AFP was significantly lower than that from non-cirrhotic cardiac ascites, likely secondary to decreased serum protein level. AFP equal to or less than 4.3g/dl could be utilized to screen for concurrent cardiac cirrhosis with high sensitivity in patients with cardiogenic ascites without other predisposing factors for liver injury.