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Nature Cancer Aug 2023Ovarian cancer (OC) is an aggressive gynecological tumor usually diagnosed with widespread metastases and ascites. Here, we depicted a single-cell landscape of the OC...
Ovarian cancer (OC) is an aggressive gynecological tumor usually diagnosed with widespread metastases and ascites. Here, we depicted a single-cell landscape of the OC ecosystem with five tumor-relevant sites, including omentum metastasis and malignant ascites. Our data reveal the potential roles of ascites-enriched memory T cells as a pool for tumor-infiltrating exhausted CD8 T cells and T helper 1-like cells. Moreover, tumor-enriched macrophages exhibited a preference for monocyte-derived ontogeny, whereas macrophages in ascites were more of embryonic origin. Furthermore, we characterized MAIT and dendritic cells in malignant ascites, as well as two endothelial subsets in primary tumors as predictive biomarkers for platinum-based chemotherapy response. Taken together, our study provides a global view of the female malignant ascites ecosystem and offers valuable insights for its connection with tumor tissues and paves the way for potential markers of efficacy evaluation and therapy resistance in OC.
Topics: Female; Humans; Ascites; CD8-Positive T-Lymphocytes; Ecosystem; Ovarian Neoplasms; Single-Cell Analysis
PubMed: 37488416
DOI: 10.1038/s43018-023-00599-8 -
The American Journal of Emergency... Aug 2023Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites and is associated with significant risk of mortality. Therefore, it... (Review)
Review
INTRODUCTION
Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites and is associated with significant risk of mortality. Therefore, it is important for emergency medicine clinicians to be aware of the current evidence regarding the diagnosis and management of this condition.
OBJECTIVE
This paper evaluates key evidence-based updates concerning SBP for the emergency clinician.
DISCUSSION
SBP is commonly due to Gram-negative bacteria, but infections due to Gram-positive bacteria and multidrug resistant bacteria are increasing. The typical presentation of SBP includes abdominal pain, worsening ascites, fever, or altered mental status in a patient with known liver disease; however, some patients may be asymptomatic or present with only mild symptoms. Paracentesis is the diagnostic modality of choice and should be performed in any patient with ascites and concern for SBP or upper gastrointestinal bleeding, or in those being admitted for a complication of cirrhosis. Ultrasound should be used to optimize the procedure. An ascites absolute neutrophil count (ANC) ≥ 250 cells/mm is diagnostic of SBP. Ascitic fluid should be placed in blood culture bottles to improve the culture yield. Leukocyte esterase reagent strips can be used for rapid diagnosis if available. While many patients will demonstrate coagulation panel abnormalities, routine transfusion is not recommended. Management traditionally includes a third-generation cephalosporin, but specific patient populations may require more broad-spectrum coverage with a carbapenem or piperacillin-tazobactam. Albumin infusion is associated with reduced risk of renal impairment and mortality.
CONCLUSIONS
An understanding of literature updates can improve the care of patients with suspected SBP.
Topics: Humans; Ascites; Liver Cirrhosis; Ascitic Fluid; Peritonitis; Emergency Medicine
PubMed: 37244043
DOI: 10.1016/j.ajem.2023.05.015 -
Gastroenterology Jan 2024Cirrhosis is a major cause of morbidity and mortality in the United States and worldwide. It consists of compensated, decompensated, and further decompensated stages;... (Review)
Review
DESCRIPTION
Cirrhosis is a major cause of morbidity and mortality in the United States and worldwide. It consists of compensated, decompensated, and further decompensated stages; median survival is more than 15 years, 2 years, and 9 months for each stage, respectively. With each stage, there is progressive worsening of portal hypertension and the vasodilatory-hyperdynamic circulatory state, resulting in a progressive decrease in effective arterial blood volume and renal perfusion. Vasoconstrictors reduce portal pressure via splanchnic vasoconstriction and are used in the management of variceal hemorrhage. Intravenous (IV) albumin increases effective arterial blood volume and is used in the prevention of acute kidney injury (AKI) and death after large-volume paracentesis and in patients with spontaneous bacterial peritonitis (SBP). The combination of vasoconstrictors and albumin is used in the reversal of hepatorenal syndrome (HRS-AKI), the most lethal complication of cirrhosis. Because a potent vasoconstrictor, terlipressin, was recently approved by the US Food and Drug Administration, and because recent trials have explored use of IV albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and IV albumin in the following 3 specific scenarios: variceal hemorrhage, ascites and SBP, and HRS.
METHODS
This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. It underwent internal peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Some of the statements are unchanged from published guidelines because of lack of new evidence in the literature. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality and evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Vasoactive drugs should be initiated as soon as the diagnosis of variceal hemorrhage is suspected or confirmed, preferably before diagnostic and/or therapeutic endoscopy. BEST PRACTICE ADVICE 2: After initial endoscopic hemostasis, vasoactive drugs should be continued for 2-5 days to prevent early rebleeding. BEST PRACTICE ADVICE 3: Octreotide is the vasoactive drug of choice in the management of variceal hemorrhage based on its safety profile. BEST PRACTICE ADVICE 4: IV albumin should be administered at the time of large-volume (>5 L) paracentesis. BEST PRACTICE ADVICE 5: IV albumin may be considered in patients with SBP. BEST PRACTICE ADVICE 6: Albumin should not be used in patients (hospitalized or not) with cirrhosis and uncomplicated ascites. BEST PRACTICE ADVICE 7: Vasoconstrictors should not be used in the management of uncomplicated ascites, after large-volume paracentesis or in patients with SBP. BEST PRACTICE ADVICE 8: IV albumin is the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with AKI. BEST PRACTICE ADVICE 9: Vasoactive drugs (eg, terlipressin, norepinephrine, and combination of octreotide and midodrine) should be used in the treatment of HRS-AKI, but not in other forms of AKI in cirrhosis. BEST PRACTICE ADVICE 10: Terlipressin is the vasoactive drug of choice in the treatment of HRS-AKI and use of concurrent albumin can be considered when accounting for patient's volume status. BEST PRACTICE ADVICE 11: Terlipressin treatment does not require intensive care unit monitoring and can be administered intravenously through a peripheral line. BEST PRACTICE ADVICE 12: Terlipressin use is contraindicated in patients with hypoxemia and in patients with ongoing coronary, peripheral, or mesenteric ischemia, and should be used with caution in patients with acute-on-chronic liver failure grade 3. The benefits may not outweigh the risks in patients with serum creatinine >5 mg/dL and in patients listed for transplantation with a Model for End-stage Liver Disease ≥35.
Topics: Humans; Terlipressin; Pharmaceutical Preparations; Octreotide; Esophageal and Gastric Varices; Ascites; End Stage Liver Disease; Gastrointestinal Hemorrhage; Severity of Illness Index; Vasoconstrictor Agents; Liver Cirrhosis; Hepatorenal Syndrome; Acute Kidney Injury; Albumins
PubMed: 37978969
DOI: 10.1053/j.gastro.2023.10.016 -
Journal of Hepatology Jul 2024Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along... (Review)
Review
Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.
Topics: Humans; Acute Kidney Injury; Liver Cirrhosis; Hepatorenal Syndrome; Ascites; Consensus
PubMed: 38527522
DOI: 10.1016/j.jhep.2024.03.031 -
Journal of Hepatology Sep 2023Further decompensation represents a prognostic stage of cirrhosis associated with higher mortality compared with first decompensation. A transjugular intrahepatic... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Further decompensation represents a prognostic stage of cirrhosis associated with higher mortality compared with first decompensation. A transjugular intrahepatic portosystemic shunt (TIPS) is indicated to prevent variceal rebleeding and for refractory ascites, but its overall efficacy to prevent further decompensations is unknown. This study assessed the incidence of further decompensation and mortality after TIPS vs. standard of care (SOC).
METHODS
Controlled studies assessing covered TIPS compared with SOC for the indication of refractory ascites and prevention of variceal rebleeding published from 2004 to 2020 were considered. We collected individual patient data (IPD) to perform an IPD meta-analysis and to compare the treatment effect in a propensity score (PS)-matched population. Primary outcome was the incidence of further decompensation and the secondary outcome was overall survival.
RESULTS
In total, 3,949 individual patient data sets were extracted from 12 controlled studies and, after PS matching, 2,338 patients with similar characteristics (SOC = 1,749; TIPS = 589) were analysed. The 2-year cumulative incidence function of further decompensation in the PS-matched population was 0.48 (95% CI 0.43-0.52) in the TIPS group vs. 0.63 (95% CI 0.61-0.65) in the SOC group (stratified Gray's test, p <0.0001), considering mortality and liver transplantation as competing events. The lower further decompensation rate with TIPS was confirmed by adjusted IPD meta-analysis (hazard ratio 0.44; 95% CI 0.37-0.54) and was consistent across TIPS indication subgroups. The 2-year cumulative survival probability was higher with TIPS than with SOC (0.71 vs. 0.63; p = 0.0001).
CONCLUSIONS
The use of TIPS for refractory ascites and for prevention of variceal rebleeding reduces the incidence of a further decompensation event compared with SOC and increases survival in highly selected patients.
IMPACT AND IMPLICATIONS
A further decompensation (new or worsening ascites, variceal bleeding or rebleeding, hepatic encephalopathy, jaundice, hepatorenal syndrome-acute kidney injury and spontaneous bacterial peritonitis) in patients with cirrhosis is associated with a poor prognosis. Besides the known role of TIPS in portal hypertension-related complications, this study shows that TIPS is also able to decrease the overall risk of a further decompensation and increase survival compared with standard of care. These results further support the role of TIPS in the management of patients with cirrhosis and portal hypertension-related complications.
Topics: Humans; Liver Cirrhosis; Portasystemic Shunt, Transjugular Intrahepatic; Ascites; Hypertension, Portal; Treatment Outcome; Esophageal and Gastric Varices
PubMed: 37141993
DOI: 10.1016/j.jhep.2023.04.028 -
Current Gastroenterology Reports Oct 2023This review summarizes the current and emerging indications, contraindications, and evaluation for TIPS. In the last three decades of use, there have been substantial... (Review)
Review
PURPOSE OF REVIEW
This review summarizes the current and emerging indications, contraindications, and evaluation for TIPS. In the last three decades of use, there have been substantial changes and progress in this field, including the use of controlled-expansion, covered stents, which has broadened the clinical uses of TIPS.
RECENT FINDINGS
Recent findings have rapidly expanded the indications for TIPS, including emerging uses in hepatorenal syndrome, hepatopulmonary syndrome and before abdominal surgery. The widespread use of controlled-expansion, covered stents has decreased rates of post-TIPS hepatic encephalopathy, opening TIPS to a larger patient population. Overall, with newer stent technology and more research in this area, the clinical utility and potential of TIPS has rapidly expanded. Going forward, a renewed focus on randomized-control trials and long-term outcomes will be a crucial element to selecting appropriate TIPS recipients and recommending emerging indications for this procedure.
Topics: Humans; Hypertension, Portal; Hepatic Encephalopathy; Stents; Contraindications; Treatment Outcome; Portasystemic Shunt, Transjugular Intrahepatic; Ascites; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage
PubMed: 37603109
DOI: 10.1007/s11894-023-00884-7