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INTRODUCTION: Pancreatic ductal adenocarcinoma is associated with significant morbidity and mortality as most patients present with advanced disease. The development of ascites has been associated with poor outcomes and further characterization and contemporary management strategies are needed. METHODS: A total of 437 patients enrolled in the Gastrointestinal Biobank at Cedars-Sinai Medical Center who had epithelial pancreatic malignancy were included in the prospective cohort group. Overall, 41.7% of patients included in this study developed ascites. Most patients with ascites (>80%) had high serum-ascites albumin gradient ascites. In both univariate and multivariate analysis, a history of ≥1 form of chemotherapy was significantly associated with ascites. Estimated median overall survival in patients with ascites was significantly lower than in patients without ascites, 473 days vs 573 days, and ascites had a hazard ratio of 1.37. RESULTS: Patients with ascites who received diuretics and indwelling peritoneal catheter had an estimated median survival of 133 days from diagnosis of ascites, and those who received only the indwelling peritoneal catheter without diuretics had an estimated median survival of only 54 days. The estimated median survival from the diagnosis of ascites was 92 days, and the median time to puncture was 7 days. The median time from first tap to death was 45 days. DISCUSSION: The use of diuretics is lower than would be expected for patients with pancreatic ductal adenocarcinoma with elevated serum-ascites albumin gradient. Other therapies such as beta blockers should be investigated in this subset of patients. The etiology of ascites in these patients is poorly understood, and further research is needed to establish treatment guidelines and improve outcomes.

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR "serotyped" (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.

Objective: The objective of this study is to develop a novel therapeutic approach for the treatment of ovarian cancer while investigating the role of tumor-infiltrating lymphocytes (TILs) in the context of ovarian cancer therapy. The primary aim is to establish a technical procedure for the isolation of tumor cells, lymphocytes, and dendritic cells (DCs) derived from ovarian cancer tissues or ascites. Subsequently, the focus lies on the generation of dendritic cell-tumor infiltrating lymphocytes (DC-TILs) exhibiting specific cytotoxic capabilities aimed at targeted therapeutic interventions. The cytotoxic impact of DC-TIL interactions on tumor cells was investigated through in vitro experimentation. This research aims to provide fundamental experimental insights for the future clinical advancement of TIL therapy in ovarian cancer. Methods: The experimental samples included fresh surgical specimens and ascites specimens procured from three patients (ranging in age from 32 to 75), sourced from the Department of Gynecology at the Third Bethune Hospital of Jilin University. TILs were extracted through in vitro isolation from solid tumor tissues, while primary tumor cells and DCs were obtained from ascites specimens. Tumor-specific antigens derived from patient tumor cells were utilized to stimulate the maturation of DCs. TILs were subsequently co-cultured with antigen-stimulated DC cells. Subsequently, TILs with specific killing effects were obtained, and the cytotoxic impact of DC-TILs on tumor cells was detected in vitro. Results: (1) TILs were successfully obtained through expansion from the tumor tissue of a patient diagnosed with ovarian cancer. (2) DCs were successfully induced from ascites cells harvested from patients diagnosed with ovarian cancer. (3) TILs significantly enhanced the cytotoxicity of tumor cells following DC stimulation. Conclusion: TILs have the capacity to augment the cytotoxicity directed towards tumor cells following DC stimulation. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Transjugular intrahepatic portosystemic shunt (TIPSS) is highly effective for treatment of variceal bleeding; however, factors contributing to rebleeding complications remain unclear.In this study, we aim to determine risk factors for recurrent portal hypertensive gastrointestinal bleeding following TIPSS.Utilising the Advancing Liver Therapeutic Approaches multicentre database, we retrospectively identified adult patients who underwent TIPSS for secondary prophylaxis of variceal bleeding and had a gastrointestinal rebleeding event within 1 year. We developed multivariable logistic regression models to identify clinical/procedural characteristics associated with rebleeding.We identified 476 patients, predominately middle‐aged (mean age 57), male (62%) and White (65%), with mean MELD‐Na 16. 16% (n = 77) had a rebleeding event; these patients were more likely to be male (p = 0.016), with higher serum creatinine (p = 0.005), MELD‐Na (p = 0.0002), portal hypertensive gastropathy on pre‐TIPSS upper endoscopy (p = 0.000) and with higher incidence of TIPSS revision (p = 0.000). There were no significant differences in type of TIPSS endoprosthesis, concurrent embolotherapy, and post‐TIPSS pressure gradients between those who experienced rebleeding and those who did not. After adjusting for TIPSS revision, multivariable analysis revealed MELD‐Na and presence of portal hypertensive gastropathy on pre‐TIPSS endoscopy were independently associated with rebleeding.In this retrospective analysis of a multicentre, nationally representative database, we found that apart from TIPSS‐related factors, high MELD‐Na and portal hypertensive gastropathy on pre‐TIPSS endoscopy were independent predictors of rebleeding within 1 year following TIPSS. These variables may be used to identify high‐risk patients who may require additional monitoring following TIPSS. [ABSTRACT FROM AUTHOR]

Introduction: Malignancy-related ascites (MRA) is a common serious complication of many advanced malignant tumors with high morbidity and mortality. The high hospital expenditures induced by unplanned readmission in patients with MRA have become an urgent issue to the public. We aimed to overall assess the unplanned early readmission rate of patients with MRA and explore the potential risk factors for such readmission. Methods: A retrospective cohort study based on 2018 Nationwide Readmissions Database was performed and patients with MRA were recruited into the analysis. The primary outcome was unplanned 30-day readmission rate and inpatient outcomes. The multivariate logistic regression analysis was performed to evaluate the potential risk factors for such early readmission. Results: Data obtained from 32,457 patients with MRA were analyzed, and of these 7,799 individuals (24.03%) were unplanned readmitted within 30-day follow-up. The mortality rate in the readmitted population was 15.15%. Patients at younger age were at a higher risk of readmission. The morbidities including hypertension (OR=1.117, 95%CI: 1.054-1.184), hyperlipemia (OR=1.075, 95%CI: 1.009-1.146) and diabetes (OR=1.118, 95%CI: 1.053-1.188), gastrointestinal malignancies and peritoneal procedure significantly increased the risk of 30-day readmission in patients with MRA. Discussion: More than one in five patients with MRA was unplanned readmitted within 30-day follow-up. The above risk factors should be timely intervened and the corresponding medical care should be strengthened in patients with MRA to lessen the unplanned readmission and improve the readmission outcomes. [ABSTRACT FROM AUTHOR]

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the effects of dietary supplementation of arginine (ARG) or guanidinoacetic acid (GAA), with or without phenylalanine (PHE), on the ascites susceptibility in the cold‐stressed broilers fed canola meal (CM)‐based diet. Method: A total of 450 one‐day‐old male broiler chicks were randomly allocated to 30 floor pens with 6 replications for each of the 5 treatments. The dietary treatments were as follows: CM‐based diet (control), CM‐based diet + 2.57 g/kg ARG, CM‐based diet + 1.8 g/kg GAA, CM‐based diet + 2.57 g/kg ARG + 1.5 g/kg PHE and CM‐based diet + 1.8 g/kg GAA + 1.5 g/kg PHE. The groups experienced cold stress induction starting at 32°C on day one, with gradual reductions to 15°C on days 21. The temperature was then held at 15°C for the remainder of the experiment. Results: The supplements ARG + PHE and GAA + PHE resulted in improved feed conversion ratios (FCR) when compared to the control group. In comparison with the control group, supplementation of ARG and ARG + PHE decreased the ascites mortality by increasing the plasma nitric oxide level (NO), blood O2 partial pressure, blood O2 saturation (SO2), and decreasing the blood CO2 partial pressure (PCO2) and right ventricle to total ventricle (RV:TV) ratio. Supplementation of GAA and GAA + PHE also declined ascites mortality by reducing blood PCO2 while increasing blood SO2 and plasma NO levels. Although plasma corticosterone level and RV:TV ratio were similar between the GAA and control groups, adding GAA + PHE significantly reduced both compared to the control group. Conclusion: In summary, supplementing cold‐stressed broiler chicken diets with 2.57 g/kg ARG may alleviate hypertension. Additionally, 1.8 g/kg GAA proves to be an effective substitute for dietary ARG in low‐ARG diets, alleviating adverse effects from cold stress. Proper PHE formulation, at 1.5 g/kg in this study, is crucial when using ARG and GAA supplements. [ABSTRACT FROM AUTHOR]

Background: There is still poor evidence about the safety and feasibility of laparoscopic liver resection (LLR) for huge (> 10 cm) hepatocellular carcinomas (HCC). The aim of this study was to assess the short- and long-term outcomes of LLR versus open liver resection (OLR) for patients with huge HCC from real-life data from consecutive patients. Methods: Data regarding all consecutive patients undergoing liver resection for huge HCC were retrospectively collected from a Korean referral HPB center. Primary outcomes were the postoperative results, while secondary outcomes were the oncologic survivals. Results: Sixty-three patients were included in the study: 46 undergoing OLR and 17 LLR. Regarding postoperative outcomes, there were no statistically significant differences in estimated blood loss, operation time, transfusions, postoperative bile leak, ascites, severe complications, and R1 resection rates. After a median follow-up of 48.4 (95% CI 8.9–86.8) months, there were no statistically significant differences in 3 years OS (59.3 ± 8.7 months vs. 85.2 ± 9.8 months) and 5 years OS (31.1 ± 9 months vs. 73.1 ± 14.1 months), after OLR and LLR, respectively (p = 0.10). Similarly, there was not a statistically significant difference in both 3 years DFS (23.5% ± 8.1 months vs. 51.6 ± months) and 5 years DFS (15.7 ± 7.1 months vs. 38.7 ± 15.3 months), respectively (p = 0.13), despite a potential clinically significant difference. Conclusion: LLR for huge HCC may be safe and effective in selected cases. Further studies with larger sample size and more appropriate design are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Objectives Patients with liver cirrhosis are prone to develop severe bacterial infections. Pharmacokinetics (PK) of antibiotics in cirrhosis are potentially affected by impaired biotransformation phases 0–3 and consequences of portal hypertension such as portovenous shunting, ascites formation and/or acute kidney injury (AKI). We aimed to elucidate to what extent PK of selected antibiotics and, therefore, dosage recommendations are affected in adults with cirrhosis. Methods We performed a systematic search in PubMed, Embase, Cochrane and CINAHL on effects of cirrhosis on PK profiles of ceftriaxone, fosfomycin, gentamicin, meropenem, nitrofurantoin, piperacillin/tazobactam and vancomycin in adults. Antibiotics were selected based on the lack of specific dosing recommendations for adults with cirrhosis. We included studies reporting on ≥1 of the following PK parameters: AUC, half-life (t ½), CL, volume of distribution (V d), peak (C max) or trough concentrations (C min). Results We identified 15 studies (ceftriaxone, n  = 5; gentamicin, n  = 3; meropenem n  = 5; vancomycin, n  = 2), including 379 patients with cirrhosis, of which two were of high quality. No eligible studies were identified for fosfomycin, nitrofurantoin or piperacillin/tazobactam. Ceftriaxone unbound concentration increased in cirrhosis, but was mitigated by increased renal CL. Gentamicin levels in ascitic fluid were comparable to those in plasma. Meropenem PK parameters were not altered in cirrhosis without AKI, but in the presence of AKI a decrease in CL was observed. In contrast, vancomycin CL decreased in advanced cirrhosis. Conclusions Available data in studies of mostly moderate quality suggest that PK of ceftriaxone, meropenem and vancomycin are altered in cirrhosis. More advanced PK studies are needed to provide specific dosing recommendations. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the efficacy and safety of ultrasound (US)-guided microwave ablation (MWA) without artificial ascites (AA) inpatients with sub-cardiac (SC) liver cancers. Methods: This retrospective study included patients with the left lobe and caudate lobe of the liver cancer who underwent US-guided MWA in our institute from January 2020 to December 2022. According to whether the target lesion was located ≤5 mm from the pericardium, patients were divided into the SC group and the non-sub-cardiac (NSC) group. In the SC group, AA was not employed during the ablation procedure. The results of technical success, technical efficiency, local tumour progression (LTP), and major complications were recorded. Results: A total of 79 patients with 87 lesions were enrolled. There were 38 patients with 38 lesions in the SC group and 41 patients with 49 lesions in the NSC group. The median follow-up of all patients was 15 (range, 3-44) months. There was no significant difference in technical success rates (100% vs 100%), technique efficiency rates (100% vs 95.7%), LTP rates (2.63% vs 0%,), and major complication rates (2.63% vs 7.32%) between the SC group and the NSC group (P > .05). No cardiac-related complications occurred. Conclusions: US-guided MWA without AA for SC liver cancers was safe and effective. Advances in knowledge: The clinical prognosis of thermal ablation without AA in the treatment of SC liver cancers is still unclear. The finding of this study provided evidence supporting the efficacy and safety of US-guided MWA without AA for treating this tricky location. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 4-month-old infant who presented to the emergency department with diarrhea, irritability, and poor reactions. Topics discussed include the infant's clinical symptoms and examination findings, abnormal laboratory results indicating metabolic disturbances, and the implications of the patient's premature birth on her overall health status.

The emergence of targeted therapies has transformed ovarian cancer treatment. However, biomarker profiling for precision medicine is limited by access to quality, tumour‐enriched tissue samples. The use of cell‐free DNA (cfDNA) in ascites presents a potential solution to this challenge. In this study, next‐generation sequencing was performed on ascites‐derived cfDNA samples (26 samples from 15 human participants with ovarian cancer), with matched DNA from ascites‐derived tumour cells (n = 5) and archived formalin‐fixed paraffin‐embedded (FFPE) tissue (n = 5). Similar tumour purity and variant detection were achieved with cfDNA compared to FFPE and ascites cell DNA. Analysis of large‐scale genomic alterations, loss of heterozygosity and tumour mutation burden identified six cases of high genomic instability (including four with pathogenic BRCA1 and BRCA2 mutations). Copy number profiles and subclone prevalence changed between sequential ascites samples, particularly in a case where deletions and chromothripsis in Chr17p13.1 and Chr8q resulted in changes in clinically relevant TP53 and MYC variants over time. Ascites cfDNA identified clinically actionable information, concordant to tissue biopsies, enabling opportunistic molecular profiling. This advocates for analysis of ascites cfDNA in lieu of accessing tumour tissue via biopsy. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cell therapy represents an attractive immunotherapy approach against recurrent epithelial ovarian cancer (EOC), as EOC is sensitive to NK cellmediated cytotoxicity. However, NK cell antitumor activity is dampened by suppressive factors in EOC patient ascites. Here, we integrated functional assays, soluble factor analysis, high-dimensional flow cytometry cellular component data and clinical parameters of advanced EOC patients to study the mechanisms of ascites-induced inhibition of NK cells. Using a suppression assay, we found that ascites from EOC patients strongly inhibits peripheral blood-derived NK cells and CD34+ progenitor-derived NK cells, albeit the latter were more resistant. Interestingly, we found that higher ascites-induced NK cell inhibition correlated with reduced progression-free and overall survival in EOC patients. Furthermore, we identified transforming growth factor (TGF)-b1 to correlate with ascites-induced NK cell dysfunction and reduced patient survival. In functional assays, we showed that proliferation and anti-tumor reactivity of CD34+ progenitor-derived NK cells are significantly affected by TGF-b1 exposure. Moreover, inhibition of TGF-b1 signaling with galunisertib partly restored NK cell functionality in some donors. For the cellular components, we showed that the secretome is associated with a different composition of CD45+ cells between ascites of EOC and benign reference samples with higher proportions of macrophages in the EOC patient samples. Furthermore, we revealed that higher TGF-b1 levels are associated with the presence of M2-like macrophages, B cell populations and T-regulatory cells in EOC patient ascites. These findings reveal that targeting TGF-b1 signaling could increase NK cell immune responses in high-grade EOC patients. [ABSTRACT FROM AUTHOR]