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1.
J Int Med Res ; 52(10): 3000605241285316, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39422049

RESUMO

Most persistent symptoms of pseudo-Meigs' syndrome (PMS) are alleviated by surgical tumor removal. The present case report suggests that PMS may present with ascites and hypercoagulation and that emergency anticoagulation can improve the patient's condition. We herein describe a postpartum woman with an acute presentation including abdominal pain, ascites, postpartum hemorrhage, and degeneration of a large uterine fibroid. Initial evaluation revealed unexpected massive ascites, pleural effusion, a highly elevated D-dimer level, and a moderately elevated CA125 level. Following anticoagulation therapy, the ascites, abdominal pain, and pleural effusion resolved. There was no recurrence of these symptoms during follow-up, although the large degenerating uterine fibroid and mildly elevated serum CA125 level persisted. Postoperatively, pathological analysis confirmed leiomyoma, the patient's CA125 level returned to normal, and the ascites resolved, meeting the diagnostic criteria for PMS. Further studies are needed to determine whether a hypercoagulable state is common in pregnant patients with PMS and to develop strategies to improve outcomes.


Assuntos
Anticoagulantes , Ascite , Antígeno Ca-125 , Síndrome de Meigs , Período Pós-Parto , Humanos , Feminino , Ascite/etiologia , Ascite/patologia , Ascite/diagnóstico , Ascite/tratamento farmacológico , Adulto , Síndrome de Meigs/diagnóstico , Anticoagulantes/uso terapêutico , Antígeno Ca-125/sangue , Gravidez , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Leiomioma/complicações , Leiomioma/cirurgia , Leiomioma/patologia , Neoplasias Uterinas/complicações , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/patologia , Proteínas de Membrana
2.
J Assoc Physicians India ; 72(9S): 32-34, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39291571

RESUMO

Hepatic edema is caused by decreased hepatic protein synthesis, a consequence of decompensated liver cirrhosis. Fluid accumulation occurs when there is an increase in hydrostatic pressure in the hepatic sinusoids and splanchnic capillaries, as well as low albumin. The first-line treatment for cirrhosis-related ascites is an aldosterone antagonist (spironolactone); however, in severe and recurring ascites, a combination of aldosterone antagonists and loop diuretics (torsemide, furosemide, and bumetanide) is preferable. Torsemide outperformed furosemide in terms of natriuretic and diuretic effects at an equivalent dose. Pharmacological features of torsemide, such as lesser hypokalemia effect, longer duration of action, higher bioavailability, and extended half-life, make it a better alternative than furosemide. In clinical studies, it is considered a safer and more acceptable choice with fewer complications.


Assuntos
Ascite , Edema , Cirrose Hepática , Inibidores de Simportadores de Cloreto de Sódio e Potássio , Torasemida , Humanos , Ascite/etiologia , Ascite/tratamento farmacológico , Edema/tratamento farmacológico , Edema/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Torasemida/farmacologia , Torasemida/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico
3.
Biomed Pharmacother ; 178: 117253, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39111084

RESUMO

Malignant ascites effusion (MAE) is a common complication of advanced malignant tumors with limited treatments. Euphorbia lathyris (EL) has a long history of application in patients with edema and ascites. Herein, we reported for the first time a mode in which EL and EL Pulveratum (PEL) spontaneously formed natural microemulsions (ELM and PELM) without the addition of any carriers and excipients, and found that the protein and phospholipid contained in them encapsulated fatty oil and diterpenoid esters through non-covalent interactions. The denaturation and degradation of protein in PELM resulted in stronger binding of diterpenoid esters to the hydrophobic region of protein, which facilitated the sustained and slow release of diterpenoid esters and improved their bioavailability in vivo, thereby retaining the efficacy of preventing MAE while alleviating the irritation of intestinal mucosa. The mechanism by which PELM retained efficacy might be related to increased feces moisture and urine volume, and decreased expression of AVPR2, cAMP, PKA and AQP3 in MAE mice. And its mechanism of reducing intestinal mucosal irritation was related to decreased cell apoptosis, amelioration of oxidative stress, elevation of mitochondrial membrane potential, and up-regulation of Occludin and Claudin-1 expression in IEC-6 cells. This nano-adjuvant-free natural microemulsions may be a promising therapeutic strategy in the field of phytochemistry for promoting the application of natural and efficient nano-aggregates spontaneously formed by medicinal plants in MAE, and provide a new perspective for advancing the development of the fusion of Chinese herbal medicine and nanomedicine and its clinical translation.


Assuntos
Emulsões , Euphorbia , Mucosa Intestinal , Euphorbia/química , Animais , Camundongos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Ascite/tratamento farmacológico , Ascite/patologia , Masculino , Apoptose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estresse Oxidativo/efeitos dos fármacos
4.
Eur J Gastroenterol Hepatol ; 36(8): 1022-1028, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38973543

RESUMO

BACKGROUND: Vasodilatation and bacterial dislocation are the main contributors to the catastrophic events in patients with decompensated liver cirrhosis (DLC). AIM: The aim of this study was to evaluate the impacts of adding midodrine and rifaximin on morbidity, mortality, and quality of life in patients with DLC. METHODS: This interventional clinical study included 100 consecutively enrolled DLC patients randomized 1 : 1 into two groups. Group A received oral midodrine (5 mg/8 h) and rifaximin (550 mg/12 h) with standard diuretic therapy, while group B received only standard diuretic therapy. Clinical and laboratory data, including the McGill Quality of Life Questionnaire, were evaluated over a 3-month treatment period. RESULTS: In the study group, there was a significant reduction in Child-Pugh and Model for End-Stage Liver Disease scores, international normalized ratio, and mean arterial blood pressure at 2, 6, and 12 weeks (P < 0.05). Ascites, spontaneous bacterial peritonitis incidence, hematemesis, paracentesis need, and hepatic encephalopathy showed improvement after 12 weeks compared with the control group. McGill Quality of Life Questionnaire significantly improved after 6 and 12 weeks (P < 0.05). Survival rates demonstrated a noteworthy improvement (P = 0.014), substantiated by evidence in both univariate and multivariate regression analyses. CONCLUSION: Combined midodrine with rifaximin represents an endowment to patients with DLC with spectacular improvements in synthetic liver functions, along with improved quality of life, and survival.


Assuntos
Cirrose Hepática , Midodrina , Qualidade de Vida , Rifamicinas , Rifaximina , Humanos , Rifaximina/uso terapêutico , Feminino , Midodrina/uso terapêutico , Midodrina/efeitos adversos , Masculino , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Cirrose Hepática/tratamento farmacológico , Pessoa de Meia-Idade , Rifamicinas/uso terapêutico , Rifamicinas/efeitos adversos , Resultado do Tratamento , Quimioterapia Combinada , Adulto , Ascite/etiologia , Ascite/tratamento farmacológico , Ascite/mortalidade , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/etiologia , Idoso , Inquéritos e Questionários , Peritonite/mortalidade , Fatores de Tempo
5.
Arq Gastroenterol ; 61: e23157, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39046001

RESUMO

BACKGROUND: The established use of non-selective beta-blockers (NSBB) in the primary and secondary prevention of esophageal varices has recently been questioned in the subgroup of patients with diuretic-refractory ascites. OBJECTIVE: Critically analyze the body of evidence on the topic in order to assist clinical decisions. METHODS: A literature review was carried out in the Pubmed® and Scielo® databases. In total, 20 articles between 2010 and 2023 were read by independent researchers. CONCLUSION: It remains doubtful whether the use of NSBB is deleterious in cirrhotic patients with refractory ascites, however our literature review allows us to conclude that these drugs should not be proscribed in these patients. On the contrary, a doctor-patient decision based on tolerability and hemodynamic parameters certainly seems to be a safe conduct.


Assuntos
Antagonistas Adrenérgicos beta , Ascite , Varizes Esofágicas e Gástricas , Cirrose Hepática , Humanos , Ascite/tratamento farmacológico , Ascite/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Varizes Esofágicas e Gástricas/tratamento farmacológico , Varizes Esofágicas e Gástricas/complicações
6.
Eur J Pharm Biopharm ; 202: 114422, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39033885

RESUMO

Malignant ascites is a common complication of advanced cancers, which reduces survival rates and diminishes patients' quality of life. Intraperitoneal chemotherapy is a conventional method for treating cancer-related ascites, but the poor drug retention of conventional drugs requires frequent administration to maintain sustained anti-tumor effects. In this study, we encapsulated doxorubicin (DOX) into Brucea javanica oil (BJO) to develop a water-in-oil (W/O) nanoemulsion called BJO@DOX for the treatment of malignant ascites through in-situ intraperitoneal administration. BJO significantly induced apoptosis of S180 cells by upregulating the expression of p53 and caspase-3 (cleaved). Additionally, BJO notably downregulated the expression of Bcl-2, further promoting apoptosis of S180 cells. Cell apoptosis significantly inhibited ascites formation and tumor cell proliferation in a mouse model. The combination of DOX and BJO exhibited satisfactory synergistic effects, consequently prolonging the survival period of mice. Histological examination of major organs indicated that the nanoemulsion had excellent biosafety in vivo. The BJO@DOX nanoemulsion represents a promising platform for in-situ chemotherapy of malignant ascites.


Assuntos
Apoptose , Ascite , Brucea , Doxorrubicina , Emulsões , Nanopartículas , Óleos de Plantas , Animais , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Ascite/tratamento farmacológico , Brucea/química , Camundongos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Nanopartículas/química , Óleos de Plantas/administração & dosagem , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Injeções Intraperitoneais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Masculino , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C
7.
Clin Transl Sci ; 17(7): e13889, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39049181

RESUMO

Esophageal and gastric varices (EGV) bleeding is a dangerous side effect of liver cirrhosis. Ascites may affect the effectiveness of carvedilol in preventing EGV rebleeding. A retrospective analysis was done on patients with EGV bleeding who visited our gastroenterology department between January 1, 2015, and October 29, 2020, and were given carvedilol therapy again. Patients were classified based on whether they had ascites. The primary outcome was EGV rebleeding. A total of 286 patients were included, with a median follow-up of 24.0 (19.0-42.0) months, comprising those without ascites (N = 155) and those with ascites (N = 131). The mean age of the patients was 55.15 ± 12.44 years, and 177 (61.9%) of them were men. There were 162 (56.6%) Child-Pugh A grades. The etiology of cirrhosis included 135 (47.2%) cases of hepatitis B. After carvedilol therapy, the patient's portal vein diameter (DPV) was widened (p < 0.05), velocity of portal vein (VPV) was slowed (p = 0.001). During the 1-year follow-up, patients with ascites had a substantially higher rebleeding rate than patients without ascites, with 24 (18.3%) versus 13 (8.4%), respectively (p = 0.013). On univariate analysis, ascites was a risk factor for rebleeding (p = 0.015). The multivariate analysis remained significant after adjusting for age, gender, etiology of cirrhosis, and previous endoscopic treatment, with OR of 2.37 (95% CI: 1.12-5.04; p = 0.025). Ascites was a risk factor for EGV rebleeding in patients undergoing carvedilol therapy. After carvedilol therapy, the patient's DPV was widened and VPV was slowed.


Assuntos
Ascite , Carvedilol , Varizes Esofágicas e Gástricas , Hemorragia Gastrointestinal , Cirrose Hepática , Humanos , Carvedilol/uso terapêutico , Carvedilol/administração & dosagem , Carvedilol/efeitos adversos , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Ascite/tratamento farmacológico , Ascite/etiologia , Estudos Retrospectivos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Idoso , Adulto , Resultado do Tratamento , Recidiva , Veia Porta
8.
Technol Cancer Res Treat ; 23: 15330338241264169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39051686

RESUMO

Objective: The prognosis of malignant tumors with peritoneal metastases and cancerous ascites has generally been poor, with limited treatment options. The PRaG regimen, which comprised of hypofractionated radiotherapy, programmed cell death-1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a survival advantage in patients with advanced solid tumors who failed at least the first line of standard systemic treatment. Intraperitoneal infusion of PD-1 inhibitors may be a novel therapeutic strategy for managing malignant ascites. Integrating the PRaG regimen with intraperitoneal perfusion of a PD-1 inhibitor might control malignant ascites and provide further survival benefits in these patients. This proposed study aims to investigate the safety and efficacy of intraperitoneal infusion of serplulimab in combination with the PRaG regimen in patients with simultaneous advanced solid tumors and cancerous ascites who fail at least the first-line treatment. Methods: This proposed study is a prospective, single-arm, open-label, multicenter clinical trial. All eligible patients will receive 2 cycles of intensive treatment, a combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor. The patients who are beneficially treated with intensive treatment will receive consolidation treatment every 2 weeks until ascites disappear, disease progression occurs, intolerable toxicity occurs, or for up to 1 year. Phase I of this study will be conducted using a modified 3 + 3 design. The dose of intraperitoneal infusion of PD-1 inhibitor for phase II will be determined according to dose-limiting toxicity evaluation in the phase I study. Conclusion: This prospective, open-label, multicenter study will potentially lead to intraperitoneal perfusion of a PD-1 inhibitor being a new strategy for malignant ascites patients and provide a meaningful efficacy and safety of the combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor for these patients.


Assuntos
Ascite , Inibidores de Checkpoint Imunológico , Infusões Parenterais , Neoplasias , Humanos , Ascite/etiologia , Ascite/tratamento farmacológico , Ascite/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Neoplasias/patologia , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Idoso , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento , Estudos Prospectivos
9.
Iran J Med Sci ; 49(6): 369-376, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38952643

RESUMO

Background: Spontaneous bacterial peritonitis (SBP) is a fatal complication of ascites fluid infection. The causes of SBP in children differ from those in adults, and these bacteria are frequently resistant to antibiotics. Therefore, this study investigated the clinical findings, bacterial etiology, and antimicrobial resistance in children with SBP. Methods: This study was conducted on all new pediatric ascites patients, who were admitted to the Department of Pediatric Gastroenterology, Namazi Hospital, affiliated with Shiraz University of Medical Sciences (Shiraz, Iran) from 2021 to 2022. Required data such as demographic information, and clinical information such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Gram staining, blood culture by Automated Blood Culture System (BACTEC), and antibiogram of ascites fluids by disc diffusion method were all collected. Finally, the data were statistically analyzed using SPSS Software (version 26). Besides, the t test, Fisher's exact, Mann-Whitney, and Chi square tests were used for data analysis. In all tests, P≤0.05 was considered statistically significant. Results: The present study examined 62 children with ascites of which 18 (29%) had SBP. The median (IQR) age was 2.5 (8.1) years. Thirty-four (54.8%) of the participants were girls. Abdominal pain was the most common clinical manifestation in patients (54%), and there was a significant association between abdominal pain and SBP (P=0.02). In 12 positive ascites fluid cultures, coagulase-negative staphylococci had the highest frequency (25%), followed by Escherichia coli (16.7%). Third-generation cephalosporins had a 25% sensitivity in the total positive cultures. This sensitivity was 33.3% for Gram-negative cultures and 16.6% for Gram-positive cultures. Conclusion: Although third-generation cephalosporins are recommended as the primary antibiotic for the empirical treatment of SBP, the present study found high bacterial resistance. Finally, empirical therapy should be tailored to each region's bacterial resistance features.


Assuntos
Antibacterianos , Peritonite , Centros de Atenção Terciária , Humanos , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Criança , Feminino , Masculino , Irã (Geográfico) , Pré-Escolar , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Centros de Atenção Terciária/estatística & dados numéricos , Centros de Atenção Terciária/organização & administração , Lactente , Adolescente , Farmacorresistência Bacteriana/efeitos dos fármacos , Ascite/tratamento farmacológico , Infecções Bacterianas/tratamento farmacológico , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/estatística & dados numéricos
10.
Hepatol Commun ; 8(7)2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38934679

RESUMO

BACKGROUND: Sodium and water retention is a mainstay of the pathophysiology leading to ascites formation in patients with advanced cirrhosis. Refractory ascites denotes the most severe ascites status with limited treatment options and a poor prognosis. We investigated the efficacy and safety of the natriuretic peptide ularitide in patients with refractory cirrhotic ascites. METHODS: We conducted a randomized placebo-controlled trial investigating ularitide to manage refractory ascites. Until trial termination after interim analyses, we randomized 17 participants in a 2:1 ratio between ularitide (n=11) and placebo (n=6). While hospitalized, the participants received treatment for up to 48 hours. The primary efficacy endpoint was a change in renal water excretion, and secondary end points included changes in renal sodium excretion rate and body weight. The starting dose was 30 ng/kg/min, though later reduced to 20 for safety reasons. RESULTS: In contrast to the study hypothesis, the mean urine production decreased after 24 hours of ularitide treatment compared with the baseline level (22.8 vs. 47.5 mL/h, p=0.04) and decreased more in participants randomized to ularitide than placebo (24.7 vs. -6.2 mL/h, p=0.05). Ularitide did not increase the renal sodium excretion rate or reduce the weight gain. The incidence rate ratio of adverse reactions in ularitide versus placebo was 8.5 (95% CI: 2-35, p=0.003). Participants treated with ularitide developed serious blood pressure reductions, impacting their renal responsiveness. CONCLUSIONS: Ularitide in doses of 20-30 ng/kg/min did not benefit urine production and renal sodium excretion rate in patients with refractory ascites. The participants randomized to ularitide overall developed more adverse reactions than placebo. EudraCT no. 2019-002268-28.


Assuntos
Ascite , Cirrose Hepática , Humanos , Masculino , Ascite/tratamento farmacológico , Ascite/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , Método Duplo-Cego , Idoso , Adulto , Sódio/urina
11.
Br J Clin Pharmacol ; 90(10): 2529-2538, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38881155

RESUMO

AIMS: Advanced chronic liver disease and advanced chronic liver disease-related ascites have a high mortality. The pharmacological treatment of ascites and fluid overload has changed little over time. Empagliflozin, a sodium-glucose cotransporter type 2 inhibitor is an untested potential novel treatment in cirrhosis, as it has survival benefits in heart failure, which has similar pathophysiological fluid overload mechanisms. Before investigating empagliflozin's potential benefit in cirrhosis, its safety must be addressed. METHODS: Ten participants (five each with compensated or decompensated advanced chronic liver disease, based on Child-Pugh class) received empagliflozin 10 mg orally daily for 4 weeks with 2 weeks follow-up. Empagliflozin safety, pharmacokinetics and pharmacodynamics were investigated. RESULTS: In total, eight patients (80%) reported an adverse event, and three patients (30%) experienced a serious adverse event, one of which was attributed to empagliflozin. Overall, the frequency of adverse events was similar to previous phase 3 trials of gliflozins. Higher plasma empagliflozin concentrations did not significantly increase the risk of adverse events. CONCLUSIONS: Four-week treatment with empagliflozin was safe and well tolerated in patients with advanced chronic liver disease. These preliminary data support assessment of long-term treatment on disease-related and mortality outcomes in patients with cirrhosis through randomized control trials.


Assuntos
Ascite , Compostos Benzidrílicos , Glucosídeos , Cirrose Hepática , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Glucosídeos/efeitos adversos , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Glucosídeos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacocinética , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/uso terapêutico , Masculino , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Pessoa de Meia-Idade , Feminino , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Ascite/tratamento farmacológico , Ascite/etiologia , Doença Crônica , Resultado do Tratamento , Adulto
12.
Liver Int ; 44(9): 2108-2113, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38934515

RESUMO

Type-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p = .016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications.


Assuntos
Ascite , Diabetes Mellitus Tipo 2 , Cirrose Hepática , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Masculino , Ascite/etiologia , Ascite/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Insulina/uso terapêutico
14.
Pancreatology ; 24(4): 616-623, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599956

RESUMO

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) therapy has been shown to improve the prognosis in patients with metastatic pancreatic cancer (PC); however, the efficacy and safety of GnP in PC patients with malignant ascites (MA) remains unknown. METHODS: We retrospectively investigated PC patients with peritoneal dissemination who had received GnP as first-line chemotherapy at our institution between March 2015 and August 2021. The following patient data were reviewed: patient characteristics, overall survival (OS), progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and relative dose intensity (RDI). The severity of MA was categorized based on the CT findings as grade 1 (small), grade 2 (moderate), or grade 3 (massive). RESULTS: A total of 189 patients were included; the study endpoints were compared between patients with each ascites grade and 41 patients without MA. The MA was classified as grade 1 in 85 patients, grade 2 in 41 patients, and grade 3 in 22 patients. In the patients with MA, the median OS, PFS and ORR were 11.2 months, 5.7 months and 24.3%, respectively. The OS and PFS decreased with increasing the severity of MA; in particular, patients with grade 2 and 3 showed a poorer prognosis. There were no differences in AEs, except for anorexia, or the RDI according to the severity of MA. CONCLUSION: GnP showed moderate efficacy with manageable safety profile in PC patients with MA. However, PC patients with moderate to massive ascites still have a dismal prognosis, and further development of effective treatments is needed.


Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Ascite , Desoxicitidina , Gencitabina , Paclitaxel , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/complicações , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Masculino , Ascite/tratamento farmacológico , Ascite/etiologia , Feminino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Idoso , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais
15.
Trials ; 25(1): 265, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627804

RESUMO

BACKGROUND: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD). METHODS/DESIGN: The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child-Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival. DISCUSSION: The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care. ETHICS AND DISSEMINATION: The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation. TRIAL REGISTRATION: EUDRACT reference number: 2018-002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019.


Assuntos
Varizes Esofágicas e Gástricas , Encefalopatia Hepática , Hipertensão Portal , Adulto , Humanos , Antagonistas Adrenérgicos beta/uso terapêutico , Ascite/tratamento farmacológico , Carvedilol/uso terapêutico , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/prevenção & controle , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/etiologia , Hipertensão Portal/complicações , Hipertensão Portal/diagnóstico , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Pragmáticos como Assunto
16.
Hepatology ; 80(3): 605-620, 2024 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-38442012

RESUMO

BACKGROUND AND AIMS: Observational studies suggest a beneficial effect of continuous terlipressin infusion (CTI) on ascites and sarcopenia in decompensated cirrhosis with portal hypertension. APPROACH AND RESULTS: This single-center, prospective, cross-over study randomized 30 patients with cirrhosis, ascites, and sarcopenia to commence on 12 weeks of home CTI or 12 weeks of observation prior to cross-over. The co-primary outcomes were change in handgrip strength and paracentesis volume. Secondary outcomes included quality of life, sarcopenia measures, renal function, safety, and hospitalization. The median age of participants was 62 years (IQR: 57-64), the median Model for End-Stage Liver Disease-Sodium was 16 (12.3-20.8), and 22 (73%) were male. Handgrip strength increased by a mean adjusted difference (MAD) of 3.09 kg (95% CI: 1.11-5.08 kg) between CTI and observation ( p =0.006); an 11.8% increase from baseline. The total volume of ascites drained decreased by a MAD of 11.39L (2.99-19.85, p =0.01), with 1.75 fewer episodes of paracentesis (0.925-2.59, p <0.001) on CTI. Serum creatinine decreased, urinary sodium excretion increased, and quality of life was significantly higher on CTI (all p <0.001), with an increase in Chronic Liver Disease Questionnaire score of 0.41 points (0.23-0.59). There were 7 minor line-related complications but no cardiac events or pulmonary edema. CONCLUSIONS: This novel study demonstrates a significant increase in handgrip strength, reduction in paracentesis volume, and improved quality of life in patients with decompensated cirrhosis treated with continuous terlipressin infusion. These findings provide a strong rationale for the use of ambulatory CTI in appropriately selected patients with cirrhosis.


Assuntos
Ascite , Estudos Cross-Over , Força da Mão , Cirrose Hepática , Terlipressina , Humanos , Masculino , Pessoa de Meia-Idade , Ascite/tratamento farmacológico , Ascite/etiologia , Terlipressina/administração & dosagem , Estudos Prospectivos , Feminino , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Infusões Intravenosas , Vasoconstritores/administração & dosagem , Sarcopenia/prevenção & controle , Sarcopenia/tratamento farmacológico , Sarcopenia/etiologia , Qualidade de Vida , Hipertensão Portal/tratamento farmacológico , Idoso
17.
BMJ Case Rep ; 17(3)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553022

RESUMO

Tularaemia is a highly infectious, zoonotic disease caused by Francisella tularensis, which has become increasingly prevalent over the past decade. Depending on the route of infection, different clinical manifestations can be observed. We report a case of typhoidal tularaemia presenting as a febrile illness with gastrointestinal symptoms in a patient in her mid-80s. During the acute illness phase and in the context of alcohol-related liver cirrhosis, the patient developed progressive ascites. During paracentesis, spontaneous bacterial peritonitis was consistently reported. Blood culture revealed Gram-negative bacilli identified as F. tularensis upon microscopic examination. Immediate clinical improvement was observed after adaptation to a pathogen-specific antibiotic regime. Typhoidal tularaemia presents general, non-specific symptoms without the local manifestations seen in other forms of the disease, thus representing a diagnostic challenge. In the case of protracted fever and if the epidemiological context as well as possible exposure are compatible, tularaemia should be considered in the differential diagnosis.


Assuntos
Francisella tularensis , Tularemia , Animais , Feminino , Humanos , Tularemia/complicações , Tularemia/diagnóstico , Tularemia/tratamento farmacológico , Ascite/diagnóstico , Ascite/etiologia , Ascite/tratamento farmacológico , Zoonoses/tratamento farmacológico , Antibacterianos/uso terapêutico
18.
Curr Oncol ; 31(3): 1477-1482, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38534945

RESUMO

Chylous ascites is a rare form of ascites with high triglyceride content arising from the thoracoabdominal lymph nodes in the peritoneal cavity due to various benign or malignant etiologies, including pancreatic cancer. During cancer chemotherapy, the accumulation of ascites can lead to the deterioration of the patient's general condition, making chemotherapy administration difficult, and resulting in a poor prognosis. We encountered a rare case of chylous ascites complicated by advanced pancreatic cancer. The patient presented with a discrepancy between the shrinkage of the pancreatic cancer and the accumulation of ascites. Therefore, we were able to promptly diagnose chylous ascites by performing biochemical tests. The patient was treated with octreotide, reportedly effective in treating chylous ascites, which rapidly improved the chylous ascites and general condition of the patient, allowing the patient to continue chemotherapy for pancreatic cancer. Therefore, physicians should consider the possibility of chylous ascites when clinically unexplained ascites are observed in patients with advanced cancer. The investigation and treatment of chylous ascites should be initiated as soon as possible.


Assuntos
Ascite Quilosa , Neoplasias Pancreáticas , Humanos , Ascite Quilosa/diagnóstico , Ascite Quilosa/etiologia , Ascite Quilosa/terapia , Ascite/complicações , Ascite/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Octreotida/uso terapêutico , Linfonodos
19.
Clin Exp Med ; 24(1): 58, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551716

RESUMO

Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is characterised by scar tissue formation, portal hypertension, and ascites (accumulation of fluid in the abdominal cavity) in decompensated cirrhosis. This review evaluates how albumin infusion ameliorates cirrhosis-associated complications. Since albumin is an oncotic plasma protein, albumin infusion allows movement of water into the intravascular space, aids with fluid resuscitation, and thereby contributes to resolving cirrhosis-induced hypovolemia (loss of extracellular fluid) seen in ascites. Thus, albumin infusion helps prevent paracentesis-induced circulatory dysfunction, a complication that occurs when treating ascites. When cirrhosis advances, other complications such as spontaneous bacterial peritonitis and hepatorenal syndrome can manifest. Infused albumin helps mitigate these by exhibiting plasma expansion, antioxidant, and anti-inflammatory functions. In hepatic encephalopathy, albumin infusion is thought to improve cognitive function by reducing ammonia concentration in blood and thereby tackle cirrhosis-induced hepatocyte malfunction in ammonia clearance. Infused albumin can also exhibit protective effects by binding to the cirrhosis-induced proinflammatory cytokines TNFα and IL6. While albumin administration has shown to prolong overall survival of cirrhotic patients with ascites in the ANSWER trial, the ATTIRE and MACHT trials have shown either no effect or limitations such as development of pulmonary oedema and multiorgan failure.  Thus, albumin infusion is not a generic treatment option for all cirrhosis patients. Interestingly, cirrhosis-induced structural alterations in native albumin (which lead to formation of different albumin isoforms) can be used as prognostic biomarkers because specific albumin isoforms indicate certain complications of decompensated cirrhosis.


Assuntos
Amônia , Ascite , Humanos , Ascite/tratamento farmacológico , Ascite/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Albuminas , Isoformas de Proteínas
20.
Anticancer Agents Med Chem ; 24(9): 668-690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305294

RESUMO

BACKGROUND: Cancer, a predominant cause of mortality, poses a formidable challenge in our pursuit of elevating life expectancy. Throughout history, individuals have sought natural remedies with minimal side effects as an appealing substitute for chemotherapeutic drugs. One such remedy is Cordyceps militaris, a renowned medicinal mushroom deeply entrenched in Asian ethnomedicine. Revered for its rejuvenating and curative attributes, it relied upon for ages. OBJECTIVE: The mushroom's soaring demand outpaced natural availability, necessitating controlled laboratory cultivation as the core focus and exploring the potential of methanolic extracts from harvested Cordyceps militaris fruiting bodies against Dalton's Lymphoma Ascites (DLA) cells in vitro, with a specific emphasis on its anticancer traits. METHODS: For cultivation, we employed a diverse range of rice substrates, among which bora rice showed promising growth of C. militaris fruiting bodies. To assess DLA cell cytotoxicity, several assays, including trypan blue exclusion assay, MTT assay, and LDH assay, were employed at different time points (24-96 h), which provided valuable insights on DLA cell viability and proliferation, shedding light on its therapeutic potential against cancer. RESULTS: Our studies unveiled that methanolic extract prompts apoptosis in DLA cells via AO/EB dual staining, manifesting consistent apoptosis indicators such as membrane blebbing, chromatin condensation, nuclei fragmentation, and cellular shrinkage at 48-96 h of treatment. Furthermore, these striking repercussions of apoptosis were comprehended by an in silico approach having molecular docking simulation against antiapoptotic proteins like BCL-2, BCL-XL, MCL-1, BFL-1 & HSP100. CONCLUSION: Methanolic C. militaris extracts exhibited cytotoxicity and apoptotic alterations in DLA cells.


Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Cordyceps , Ensaios de Seleção de Medicamentos Antitumorais , Linfoma , Cordyceps/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linfoma/tratamento farmacológico , Linfoma/patologia , Relação Dose-Resposta a Droga , Animais , Humanos , Relação Estrutura-Atividade , Ascite/patologia , Ascite/tratamento farmacológico , Células Tumorais Cultivadas , Sobrevivência Celular/efeitos dos fármacos , Estrutura Molecular , Camundongos , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular
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