Case report: Rapid development of acute symptomatic portal vein system thrombosis after endoscopic variceal therapy in a patient with liver cirrhosis.

Acute portal vein thrombosis (PVST), a serious complication of liver cirrhosis, is characterized as abdominal pain secondary to intestinal ischemia, and even intestinal necrosis. Anticoagulation is recommended for the treatment of acute PVST, but is often postponed in cirrhotic patients with acute variceal bleeding or those at a high risk of variceal bleeding. Herein, we reported a 63-year-old male with a 14-year history of alcoholic liver cirrhosis who developed progressive abdominal pain related to acute portal vein and superior mesenteric vein thrombosis immediately after endoscopic variceal ligation combined with endoscopic cyanoacrylate glue injection for acute variceal bleeding. Fortunately, acute PVST was successfully recanalized by the use of low molecular weight heparin. Collectively, this case suggests that acute symptomatic PVST can be secondary to endoscopic variceal therapy in liver cirrhosis, and can be safely and successfully treated by anticoagulation.

Therapeutic roles of platelet-rich plasma to restore female reproductive and endocrine dysfunction.

Millions of women worldwide are infertile due to gynecological disorders, including premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometrial atrophy, and fallopian tube obstruction. These conditions frequently lead to infertility and have a substantial impact on the quality of life of the affected couples, primarily because of their psychological implications and high financial costs. Recently, using platelets to stimulate cell proliferation and tissue differentiation has emerged as a promising approach in regenerative medicine. Platelet-rich plasma (PRP) shows considerable potential for promoting endometrial hypertrophy and follicle development, making it a promising therapeutic option for tissue repair or replacement. This review provides an overview of the recent advancements and underlying mechanisms of PRP therapy for various female reproductive diseases and presents new therapeutic options for addressing female infertility.

Association of echocardiography-related parameters with the prognosis of decompensated cirrhosis: a retrospective cohort study.

BACKGROUND: Cardiac morphology and function, which are conventionally evaluated by echocardiography, are often abnormal in decompensated cirrhosis. We aimed to evaluate the association of echocardiography-related parameters with prognosis in cirrhosis. METHODS: This retrospective study included 104 decompensated cirrhotic patients, in whom cardiac structure and function were measured by echocardiography, including mitral inflow early diastolic velocity/mitral inflow late diastolic velocity (E/A), left atrium diameter, left ventricular end-diastolic dimension, interventricular septal thickness, left ventricular posterior wall thickness, right atrial transverse diameter, right atrial longitudinal diameter, right ventricular dimension (RVD), stroke volume, cardiac output, left ventricular ejection fraction, and fractional shortening. Cox regression and competing risk analyses and Kaplan-Meier and Nelson-Aalen cumulative risk curves were used to evaluate their associations with further decompensation and death in cirrhotic patients, if appropriate. RESULTS: Lower RVD was a predictor of further decompensation in Cox regression (adjusted by Child-Pugh score: p = 0.138; adjusted by MELD score: p = 0.034) and competing risk analyses (p = 0.003), and RVD ≤17 mm was significantly associated with higher cumulative incidence of further decompensation in Kaplan-Meier (p = 0.002) and Nelson-Aalen cumulative risk curves (p = 0.002). E/A ≤ 0.8 was a significant predictor of death in Cox regression (adjusted by Child-Pugh score: p = 0.041; adjusted by MELD score: p = 0.045) and competing risk analyses (p = 0.024), and E/A ≤ 0.8 was significantly associated with higher cumulative incidence of death in Kaplan-Meier (p = 0.023) and Nelson-Aalen cumulative risk curves (p = 0.024). Other echocardiography-related parameters were not significantly associated with further decompensation or death. CONCLUSION: RVD and E/A may be considered for the prognostic assessment of decompensated cirrhosis.

Association of non-selective ß blockers with the development of renal dysfunction in liver cirrhosis: a systematic review and meta-analysis.

BACKGROUND & AIMS: Non-selective ß blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output. This study aimed to systematically investigate their association. METHODS: PubMed, EMBASE, and Cochrane library databases were searched to identify all relevant studies evaluating the association of NSBBs with renal dysfunction in cirrhotic patients. Unadjusted and adjusted data were separately extracted. Odds ratios (ORs) and hazard ratios (HRs) were pooled. Subgroup meta-analyses were performed according to the proportions of ascites and Child-Pugh class B/C and the mean model for end-stage liver disease (MELD) score. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS: Fourteen studies were finally included. Based on unadjusted data, NSBBs significantly increased the risk of developing renal dysfunction (OR = 1.49; p = 0.03), and this association remained significant in subgroup analyses of studies where the proportions of ascites was >70% and Child-Pugh class B/C was 100%. Based on adjusted data with propensity score matching (adjusted OR = 0.61; p = 0.08) and multivariable regression modelling (adjusted HR = 0.86; p = 0.713), NSBBs did not increase the risk of developing renal dysfunction, and this association remained not significant in subgroup analyses of studies where the proportions of ascites was >70% and <70%, the proportion of Child-Pugh class B/C was <100%, and the mean MELD score was <15. The quality of evidence was very low for all meta-analyses. CONCLUSIONS: NSBBs may not be associated with the development of renal dysfunction in liver cirrhosis. However, more evidence is required to clarify their association in specific populations.

Non-selective ß blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output in liver cirrhosis.Our meta-analysis failed to support the association of NSBBs with an increased risk of developing renal dysfunction after covariate adjustment.

Anticoagulation Therapy for Splanchnic Vein Thrombosis Associated With Acute Pancreatitis: A Systematic Review and Meta-Analysis.

Splanchnic vein thrombosis (SVT) is not rare in patients with acute pancreatitis. It remains unclear about whether anticoagulation should be given for acute pancreatitis-associated SVT. The PubMed, EMBASE, and Cochrane Library databases were searched. Rates of SVT recanalization, any bleeding, death, intestinal ischemia, portal cavernoma, and gastroesophageal varices were pooled and compared between patients with acute pancreatitis-associated SVT who received and did not receive therapeutic anticoagulation. Pooled rates and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Heterogeneity among studies was evaluated. Overall, 16 studies including 698 patients with acute pancreatitis-associated SVT were eligible. After therapeutic anticoagulation, the pooled rates of SVT recanalization, any bleeding, death, intestinal ischemia, portal cavernoma, and gastroesophageal varices were 44.3% (95%CI = 32.3%-56.6%), 10.7% (95%CI = 4.9%-18.5%), 13.3% (95%CI = 6.9%-21.4%), 16.8% (95%CI = 6.9%-29.9%), 21.2% (95%CI = 7.5%-39.5%), and 29.1% (95%CI = 16.1%-44.1%), respectively. Anticoagulation therapy significantly increased the rate of SVT recanalization (RR = 1.69; 95%CI = 1.29-2.19; P < .01), and marginally increased the risk of bleeding (RR = 1.98; 95%CI = 0.93-4.22; P = .07). The rates of death (RR = 1.42; 95%CI = 0.62-3.25; P = .40), intestinal ischemia (RR = 2.55; 95%CI = 0.23-28.16; P = .45), portal cavernoma (RR = 0.51; 95%CI = 0.21-1.22; P = .13), and gastroesophageal varices (RR = 0.71; 95%CI = 0.38-1.32; P = .28) were not significantly different between patients who received and did not receive anticoagulation therapy. Heterogeneity was statistically significant in the meta-analysis of intestinal ischemia, but not in those of SVT recanalization, any bleeding, death, portal cavernoma, or gastroesophageal varices. Anticoagulation may be effective for recanalization of acute pancreatitis-associated SVT, but cannot improve the survival. Randomized controlled trials are warranted to further investigate the clinical significance of anticoagulation therapy in such patients.

Treatment and outcomes of immune checkpoint inhibitors-associated colitis/diarrhea: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved the outcomes of cancer patients. However, ICIs often lead to colitis/diarrhea. This study aimed to assess the treatment of ICIs-associated colitis/diarrhea and outcomes. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies which investigated the treatment and outcomes of colitis/diarrhea developing in patients who received ICIs. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea as well as the pooled rates of response to treatment, mortality, and ICIs permanent discontinuation and restarts in patients with ICIs-associated colitis/diarrhea were estimated using a random-effects model. RESULTS: Among the 11,492 papers initially identified, 27 studies were included. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea were 17%, 3%, 17%, 13%, and 15%, respectively. The pooled rates of overall response, response to corticosteroid therapy, and response to biological agents were 88%, 50%, and 96%, respectively. The pooled short-term mortality in patients with ICIs-associated colitis/diarrhea was 2%. The pooled incidences of ICIs permanent discontinuation and restarts were 43% and 33%, respectively. CONCLUSION: ICIs-associated colitis/diarrhea is common, but rarely lethal. Half of them are responsive to corticosteroid therapy. There is a fairly high rate of response to biological agents in steroid-refractory colitis/diarrhea patients.

Incidence and outcomes of pancreatic encephalopathy in patients with acute pancreatitis: a systematic review and meta-analysis.

Pancreatic encephalopathy (PE) is a lethal complication of acute pancreatitis (AP), but its clinical characteristics and prognosis remain obscure. Herein, we performed a systematic review and meta-analysis to evaluate the incidence and outcomes of PE in AP patients. PubMed, EMBASE, and China National Knowledge Infrastructure were searched. Based on the data from cohort studies, the incidence and mortality of PE in AP patients were pooled. Based on the individual data from case reports, logistic regression analyses were performed to identify the risk factors for death in PE patients. Among 6702 papers initially identified, 148 were included. Based on 68 cohort studies, the pooled incidence and mortality of PE in AP patients were 11% and 43%, respectively. The causes of death were clearly reported in 282 patients, of which the most common was multiple organ failure (n = 197). Based on 80 case reports, 114 AP patients with PE were included. The causes of death were clearly reported in 19 patients, of which the most common was multiple organ failure (n = 8). Univariate analyses showed that multiple organ failure (OR = 5.946; p = 0.009) and chronic cholecystitis (OR = 5.400; p = 0.008) were the significant risk factors of death among patients with PE. PE is not a rare complication of AP and indicates poor prognosis. Such a high mortality of PE patients may be attributed to its coexistence of multiple organ failure.

Incidence and outcomes of splanchnic vein thrombosis after diagnosis of COVID-19 or COVID-19 vaccination: a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) and COVID-19 vaccination may cause splanchnic vein thrombosis (SVT), which is potentially fatal. The present study aims to pool the incidence and outcomes of SVT patients with COVID-19 or having received COVID-19 vaccines. The PubMed, EMBASE, and Cochrane databases were searched. Based on the data from cohort studies, meta-analyses were performed to evaluate the incidence of SVT in COVID-19 patients or people having received COVID-19 vaccines. Pooled proportions were calculated. Based on the individual data from case reports, logistic regression analyses were performed to identify factors associated with death in SVT patients. Odds ratios (ORs) were calculated. Among 654 papers initially identified, 135 were included. Based on 12 cohort studies, the pooled incidence of SVT in COVID-19 patients was 0.6%. Data were insufficient to estimate the incidence of SVT after COVID-19 vaccination. Based on 123 case reports, the mortality was 14% (9/64) in SVT patients with COVID-19 and 25% (15/59) in those who received COVID-19 vaccines. Univariate analyses demonstrated that age (OR = 1.061; p = 0.017), diabetes mellitus (OR = 14.00; p = 0.002), anticoagulation (OR = 0.098; p = 0.004), and bowel resection (OR = 16.00; p = 0.001) were significantly associated with death in SVT patients with COVID-19; and anticoagulation (OR = 0.025; p = 0.003) and intravenous immunoglobulin (OR = 0.175; p = 0.046) were significantly associated with death in SVT patients who received COVID-19 vaccines. Multivariate analyses did not identify any independent factor for death in both patients. SVT in COVID-19 patients and in subjects who received COVID-19 vaccines carries a high mortality, but may be improved by anticoagulation. PROSPERO Identifier CRD42022315254.

Efficacy and Safety of PD-1/PD-L1 Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

INTRODUCTION: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly employed for the treatment of various cancers in clinical practice. This study aimed to systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitors for advanced hepatocellular carcinoma (HCC). METHODS: PubMed, EMBASE, Cochrane library, Web of Science, and Abstracts of American Society of Clinical Oncology proceedings databases were searched. Objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), median overall survival (OS), and incidence of adverse events (AEs) and drug withdrawal were pooled. Odds ratio (OR) and hazard ratio (HR) were calculated to analyze the difference in the ORR, DCR, PFS, and OS between groups. RESULTS: Among the 14,902 initially identified papers, 98 studies regarding use of PD-1/PD-L1 inhibitors in advanced HCC were included. Based on different criteria of response in solid tumors, the pooled ORR, DCR, and median PFS was 16-36%, 54-74%, and 4.5-6.8 months, respectively. The pooled median OS was 11.9 months. Compared to multitarget tyrosine kinase inhibitors (TKIs), PD-1/PD-L1 inhibitors monotherapy significantly increased ORR (OR 2.73, P < 0.00001) and OS (HR 0.97, P = 0.05), and PD-1/PD-L1 inhibitors combined with TKIs significantly increased ORR (OR 3.17, P < 0.00001), DCR (OR 2.44, P < 0.00001), PFS (HR 0.58, P < 0.00001), and OS (HR 0.58, P < 0.00001). The pooled incidence of all-grade AEs, grade ≥ 3 AEs, and drug withdrawal was 71%, 25%, and 7%, respectively. CONCLUSION: On the basis of the present systematic review and meta-analysis, PD-1/PD-L1 inhibitors should be the preferred treatment choice for advanced HCC owing to their higher antitumor effect and improved outcomes.

Efficacy and safety of thrombolytic therapy for portal venous system thrombosis: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The role of thrombolytic therapy in patients with portal venous system thrombosis (PVST) remains ambiguous. This study aimed to systematically collect available evidence and evaluate the efficacy and safety of thrombolysis for PVST. METHODS: Eligible studies were searched via PubMed, EMBASE, and Cochrane Library databases. Among the cohort studies, meta-analyses were performed to assess the outcomes of PVST patients receiving thrombolysis. Pooled proportions were calculated. Among the case reports and case series, logistic regression analyses were performed to identify the risk factors for outcomes of PVST patients receiving thrombolysis. Odds ratios (ORs) were calculated. RESULTS: Among the 2134 papers initially identified, 29 cohort studies and 131 case reports or case series were included. Based on the cohort studies, the pooled rates of overall response to thrombolytic therapy, complete recanalization of PVST, bleeding events during thrombolysis, further bowel resection, thrombosis recurrence, and 30-day mortality were 93%, 58%, 18%, 3%, 1%, and 4%, respectively. Based on the case reports and case series, acute pancreatitis (OR = 0.084), history of liver transplantation (OR = 13.346), and interval between onset of symptoms and initiation of thrombolysis ≤14 days (OR = 3.105) were significantly associated with complete recanalization of PVST; acute pancreatitis (OR = 6.556) was significantly associated with further bowel resection; but no factors associated with the overall response to thrombolytic therapy, bleeding events during thrombolysis, thrombosis recurrence, and 30-day mortality were identified or could be calculated. CONCLUSION: Early initiation of thrombolysis should be effective for the treatment of PVST. But its benefits for PVST secondary to acute pancreatitis are weakened.

Successful treatment of acute symptomatic extensive portal venous system thrombosis by 7-day systemic thrombolysis.

Acute portal venous system thrombosis (PVST) can cause acute mesenteric ischemia and even intestinal infarction, which are potentially fatal, and requires recanalization in a timely fashion. Herein, we report a 56-year-old man with acute non-cirrhotic symptomatic extensive PVST who achieved portal vein recanalization after systemic thrombolysis combined with anticoagulation. Initially, anticoagulation with enoxaparin sodium for 4 d was ineffective, and then systemic thrombolysis for 7 d was added. After that, his abdominal pain completely disappeared, and portal vein system vessels became gradually patent. Long-term anticoagulation therapy was maintained. In conclusion, 7-d systemic thrombolysis may be an effective and safe choice of treatment for acute symptomatic extensive PVST which does not respond to anticoagulation therapy.

Epidemiology of portal vein thrombosis in liver cirrhosis: A systematic review and meta-analysis.

BACKGROUND: Portal vein thrombosis (PVT) may be associated with negative outcomes in patients with liver cirrhosis. However, the prevalence and incidence of PVT in liver cirrhosis are heterogeneous among studies and have not been sufficiently determined yet. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched. Eligible studies would explore the prevalence and/or incidence of PVT in liver cirrhosis without hepatocellular carcinoma or abdominal surgery. Pooled proportion with 95% confidence interval (CI) was calculated using a random-effect model. Factors associated with the presence/occurrence of PVT were also extracted. RESULTS: Among the 8549 papers initially identified, 74 were included. Fifty-four studies explored the prevalence of PVT in liver cirrhosis with a pooled prevalence of 13.92% (95%CI=11.18-16.91%). Based on cross-sectional data, Child-Pugh class B/C, higher D-dimer, ascites, and use of non-selective beta-blockers (NSBBs) were associated with the presence of PVT in liver cirrhosis. Twenty-three studies explored the incidence of PVT in liver cirrhosis with a pooled incidence of 10.42% (95%CI=8.16-12.92%). Based on cohort data, Child-Pugh class B/C, higher model of end-stage liver disease score, higher D-dimer, lower platelets count, decreased portal flow velocity, ascites, use of NSBBs, and moderate or high-risk esophageal varices could predict the occurrence of PVT in liver cirrhosis. CONCLUSION: Approximately one seventh of cirrhotic patients have PVT, and one tenth will develop PVT. Progression of liver cirrhosis and portal hypertension seems to be in parallel with the risk of PVT. Prospective studies with detailed information about classification and extension of PVT in liver cirrhosis are needed.