ADAMTS-13/von Willebrand factor ratio: A prognostic biomarker for portal vein thrombosis in compensated cirrhosis. A prospective observational study

Background and aimsIn cirrhosis, decreased portal flow velocity, thrombophilia factors, and portal hypertension are considered risk factors for portal vein thrombosis (PVT). In cirrhosis, the transformation of the stellate cells causes a progressive decrease of ADAMTS-13, while VWF multimers secretion by endothelial cells is strongly enhanced. This imbalance leads to an accumulation of ultra-large VWF multimers that in sinusoidal circulation could favor PVT both in intra- and extra-hepatic branches, mostly in decompensated cirrhosis. This prospective study was aimed at identifying possible clinical, biochemical, and hemostatic factors predictive for non-tumoral PVT in a cohort of patients with compensated cirrhosis.MethodsSeventynine compensated cirrhosis patients were prospectively followed for 48 months, receiving a periodic Doppler-ultrasound liver examination associated with an extensive evaluation of clinical, biochemical, and hemostatic profile.ResultsFive patients developed PVT (cumulative prevalence = 6.3%), occurring 4–36 months after enrollment. In logistic regression analysis, the ADAMTS-13/VWF:GpIbR ratio < 0.4 was the only independent variable significantly associated with PVT (OR 14.6, 95% C.I.:1.36–157.2, p = 0.027). A Cox-regression-analysis confirmed this finding (HR = 7.7, p = 0.027).ConclusionsThe ADAMTS-13/VWF ratio < 0.4 measured in compensated cirrhosis could be a reliable predictive biomarker for PVT development, paving the way to novel therapeutic strategies to prevent and treat PVT in this clinical setting.     

Effect of portal vein thrombosis on the prognosis of patients with cirrhosis without a liver transplant: A systematic review and meta-analysis

Background:Portal vein thrombosis (PVT) is a relatively common complication of cirrhosis. However, the effect of PVT on the prognosis might not be unequivocal. A systematic review and meta-analysis were performed to investigate the effect of PVT on the prognosis of patients with cirrhosis who have not received a liver transplant.Methods:Three databases, including PubMed, EMBASE, and Cochrane Library, were searched for studies published up to March 2020. The survival or mortality rate of patients with PVT served as the main index to evaluate the prognosis of these patients. Hepatic decompensation served as the index of disease progression. Meta-analyses were conducted using Review Manager software 5.2.Results:Sixteen clinical studies were included and analyzed. PVT was associated with an increased risk of mortality in patients with decompensated cirrhosis. According to the meta-analysis, patients with cirrhosis presenting with PVT had a lower 1-year survival rate than patients without PVT (odds ratio (OR), 0.32; 95% confidence interval (CI), 0.14–0.75; P = .008). The cumulative survival rates were similar between the 2 groups at 3 years (OR, 1.04; 95% CI, 1.00–1.08; P = .06), 5 years (OR, 1.33; 95% CI, 0.71–2.48; P = .38) and 10 years (OR, 1.24; 95% CI, 0.79–1.93; P = .35). PVT was associated with a higher mortality rate in patients with Child-Pugh class B and C disease. A significantly increased risk of death was observed in patients with complete PVT. Patients with both PVT and cirrhosis had a higher rate of decompensation than patients without PVT.Conclusions:The presence of PVT might exert a slight effect on the overall prognosis of patients with cirrhosis. PVT might mainly affect the short-term prognosis by increasing hepatic decompensation events in patients with cirrhosis. However, PVT might not influence the long-term prognosis of patients with cirrhosis.     

Preservation of platelet function in patients with cirrhosis and thrombocytopenia undergoing esophageal variceal ligation

BackgroundThrombocytopenia is a possible risk factor for bleeding after band ligation of esophageal varices. However, elevated von Willebrand factor (VWF) in cirrhosis improves platelet function and could decrease this risk. Our objective was to assess platelet function in patients with cirrhosis undergoing esophageal variceal ligation (EVL).MethodsThe assessment consisted of platelet count, antigen and activity of VWF and VWF-cleaving protease ADAMTS-13 activity, and a platelet adhesion and aggregation test simulating vascular flow in vivo (Impact-R^Ⓡ) prior to EVL.ResultsTotally 111 patients were divided into three groups according to platelet count: (1) < 50 × 10⁹/L (n = 38, 34.2%); (2) 50 × 10⁹/L to 100 × 10⁹/L (n = 47, 42.3%); and (3) > 100 × 10⁹/L (n = 26, 23.4%). No statistically significant difference was found in the aggregate size of platelets [group 1: 41.0 (31.8–67.3) µm²; group 2: 47.0 (33.8–71.3) µm²; and group 3: 47.0 (34.0–66.0) µm²; P = 0.60] and no significant correlation was found between aggregate size and platelet count (Spearman r = 0.07; P = 0.47). Surface coverage was 4.1% (2.8%–6.7%), 8.5% (4.0%–10.0%), and 9.0% (7.1%–12.0%) (P < 0.001) in groups 1, 2 and 3, respectively and correlated with platelet count (Spearman r = 0.39; P < 0.0001). There was no significant difference between groups in VWF or ADAMTS-13. Post-EVL bleeding occurred in six (5.4%) patients (n = 2 in group 1, n = 1 in group 2, and n = 3 in group 3; P = 0.32). Patients with bleeding had higher MELD scores [15.0 (11.3–20.3) versus 12.0 (10.0–15.0); P = 0.025], but no difference was demonstrated for platelet function parameters.ConclusionPlatelet function is preserved even in the presence of thrombocytopenia, including in the patients with post-EVL bleeding.     

Efficacy and safety of direct oral anticoagulants versus vitamin K antagonist for portal vein thrombosis in cirrhosis: A systematic review and meta-analysis

Introduction and aimPortal vein thrombosis (PVT) is associated with a higher risk of liver-related complications. Recent guidelines recommend direct-acting anticoagulants (DOAC) in patients with cirrhosis and non-tumoral PVT. However, data on the efficacy and safety of DOAC in these patients remain limited. We aim to investigate the efficacy and safety of DOAC compared to vitamin K antagonists (VKA) to treat non-tumoral PVT in patients with cirrhosis.MethodsWe performed a systematic search of six electronic databases using MeSH term and free text. We selected all studies comparing the use of DOACs with vitamin K antagonist to treat PVT in cirrhosis. The primary outcome was PVT recanalization. Secondary outcomes were and PVT progression, major bleeding, variceal bleeding and death.ResultsFrom 944 citations, we included 552 subjects from a total of 11 studies (10 observational and 1 randomized trial) that fulfilled the inclusion criteria. We found that DOAC were associated with a higher pooled rate of PVT recanalization (RR = 1.67, 95%CI: 1.02, 2.74, I² = 79%) and lower pooled risk of PVT progression (RR = 0.14, 95%CI: 0.03–0.57, I² = 0%). The pooled risk of major bleeding (RR = 0.29, 95%CI: 0.08–1.01, I² = 0%), variceal bleeding (RR = 1.29, 95%CI: 0.64–2.59, I² = 0%) and death (RR = 0.31, 95%CI: 0.01–9.578, I² = 80%) was similar between DOAC and VKA.ConclusionFor the treatment of PVT in patients with cirrhosis, the bleeding risk was comparable between DOAC and VKA. However, DOAC were associated with a higher pooled rate of PVT recanalization. Dedicated randomized studies are needed to confirm these findings.     

Clinical Validation of Global Coagulation Tests to Guide Blood Component Transfusions in Cirrhosis and ACLF

Background and AimsPatients with cirrhosis and acute-on-chronic liver failure (ACLF) may have bleeding complications and need for invasive procedures. Point-of-care (POC) coagulation tests like thromboelastography (TEG) and Sonoclot may be better for guiding patient management than the standard coagulation tests (SCTs), like prothrombin time, platelet count and international normalized ratio.MethodsWe prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion requirements. We assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC strategy.ResultsEpisodes of bleeding were seen in 45% and 28% of ACLF and cirrhosis patient, respectively (p=0.036), with the major site of bleeding being gastrointestinal (31% and 16%, respectively). Platelet counts correlated with TEG-maximum amplitude in cirrhosis (p=0.045) and prothrombin time correlated positively with TEG-reaction (R) time (p=0.032), TEG-Clot kinetics (K) time (p=0.042), Son-activated clotting time (p=0.038) and negatively with clot rate (p=0.043) in ACLF, making these correctable target variables in POC transfusion algorithms. Of 223 procedures, transfusion of fresh frozen plasma and platelet concentrate was reduced by 25% (p=0.035) and 20.8% (p=0.045) by using a POC strategy in 76 patients. Correction of deranged Son-activated clotting time and TEG-reaction time was noted in 68% and 72% after 24 h of fresh frozen plasma transfusion in ACLF and 85% and 80% in cirrhosis, respectively.ConclusionsOur study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis, whereas use of conventional tests appear to be less suitable in patients with clinical bleeding.Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT04332484","term_id":"NCT04332484"}}NCT04332484.     

Impact of Inpatient Attending Specialty and Gastroenterology Consultation on Quality of Care of Patients Hospitalized with Decompensated Cirrhosis

BackgroundData suggest hospitalists are less adherent to quality indicators for decompensated cirrhosis, and gastroenterology consultation may improve adherence. We sought to evaluate the impact of inpatient attending specialty and gastroenterology consultation on quality of care for decompensated cirrhosis.MethodsThis was a retrospective cohort study of patients with decompensated cirrhosis admitted to gastroenterology or hospitalist service at the University of Michigan between 2016-2020. The primary outcome was adherence to nationally recommended inpatient quality indicators for ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and gastrointestinal bleeding. Performance was calculated per patient admission as the proportion of quality indicators met vs quality indicators for which the patient was eligible. Quality indicator scores were compared between services using t-tests. We also evaluated the effect of gastroenterology consultation on quality indicator scores for patients admitted to hospitalist service. Clinical outcomes were compared using multivariable models adjusted for patient characteristics.ResultsTwo hundred eighty-eight admissions were included (155 to gastroenterology service; 133 to hospitalist service). Quality indicator score for all admissions was 69.9% (standard deviation [SD] ± 24.2%). Quality indicator scores were similar between gastroenterology (69.9%, SD ± 23.6%) and hospitalist (69.8%, SD ± 25.1%) services (P = .913). There was no difference in quality indicator subscores for each complication between services. Hospitalists placed a gastroenterology consultation in 53.4% of admissions, and it was associated with higher albumin administration for patients with spontaneous bacterial peritonitis (57.1% vs 25%, P = .044). Patients admitted to gastroenterology service had higher readmissions within 30 days (adjusted odds ratio = 1.95) and shorter length of hospitalization (adjusted rate ratio = 0.85).ConclusionsHospitalists provided comparable quality of care to gastroenterologists for inpatients with decompensated cirrhosis.     

Clinical outcomes of acute pancreatitis in patients with cirrhosis

BackgroundAP outcomes in cirrhotic patients have not yet been studied. We aim to investigate the outcomes of cirrhotics patients with acute pancreatitis.MethodsThe National Inpatient Sample (NIS) database (2003–2013) was queried for patients with a discharge diagnosis of AP and liver cirrhosis. Cirrhosis was further classified as compensated and decompensated using the validated Baveno IV criteria. Primary outcome was inpatient mortality. The analysis was adjusted for age, gender, race, Charlson comorbidity index (CCI), median income quartile, and hospital characteristics.ResultsOver 2.8 million patients with acute pancreatitis were analyzed. Cirrhosis prevalence was 2.8% (80,093). Both compensated and decompensated cirrhosis subjects had significantly higher mortality. Highest odds ratios (OR) were: inpatient mortality (OR 3.4, P < 0.001), Shock (OR 1.5, P = 0.02), Ileus (OR: 1.3, p = 0.02, ARDS (OR 1.2, p = 0.03), upper endoscopy performed (OR 2.0, p < 0.001), blood transfusions (OR 3.1, p < 0.001), gastrointestinal bleed (OR 5.5, p < 0.001), sepsis (OR 1.3, p = 0.005), portal vein thrombosis (PVT) (OR 7.2, p < 0.001), acute cholecystitis (OR 1.3, p < 0.001). Interestingly, cirrhosis patients had lower hospital length of stay, (OR 0.16, p < 0.001), AKI (OR 0.93, p = 0.06), myocardial infarction (OR 0.31, p < 0.001), SIRS (OR 0.62, p < 0.001), parenteral nutrition requirement (OR 0.84, p = 0.002). Decompensated cirrhosis had higher inflation-adjusted hospital charges (+$3896.60; p < 0.001).ConclusionAP patients with cirrhosis have higher inpatient mortality, but it is unlikely to be due to AP severity as patients had lower incidence of SIRS and AKI. Higher mortality is possibly related to complications of cirrhosis and portal hypertension itself such as GI bleed, shock, PVT, AC and sepsis.     

Prognostic Impact of Combined Late Gadolinium Enhancement on Cardiovascular Magnetic Resonance and Peak Oxygen Consumption in Ambulatory Patients With Nonischemic Dilated Cardiomyopathy

BackgroundPeak oxygen consumption (peak VO₂) and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) are prognostic in heart failure. We investigated whether LGE-CMR and peak VO₂ combined had additive value in risk stratifying patients with nonischemic dilated cardiomyopathy (DCM).Methods and ResultsFifty-seven DCM patients underwent CMR and cardiopulmonary exercise testing. Cardiac events were cardiac death, hospitalization for decompensated heart failure, or lethal arrhythmia. Twenty-five (44%) were LGE-positive. The median peak VO₂ was 18.5 mL·kg^-1·min^-1. On multivariate analysis, positive LGE (P = .048) and peak VO₂ (P = .003) were independent cardiac event predictors. Cardiac event risk was significantly higher with positive LGE and peak VO₂ < 18.5 mL·kg^-1·min^-1 than with negative LGE and peak VO₂ ≥ 18.5 mL·kg^-1·min^-1 (hazard ratio 12.5; 95% CI 1.57–100; P = .017). In 3 patient groups (group A: no LGE, peak VO₂ ≥ 18.5 mL·kg^-1·min^-1, n = 18; group B: positive LGE or peak VO₂ < 18.5 mL·kg^-1·min^-1, n = 24; group C: positive LGE and peak VO₂ < 18.5 mL·kg^-1·min^-1, n = 15) during follow-up (71 ± 32 months), group C had higher cardiac event rates than the others.ConclusionsCombined assessment of LGE-CMR and peak VO₂ provides additive prognostic information in ambulatory DCM.     

Fibrinogen function is impaired in whole blood from patients with cyanotic congenital heart disease

Background

Patients with cyanotic congenital heart disease (CCHD) have haemostatic abnormities associated with bleeding and thrombo-embolic events. The haemostatic abnormalities are not fully understood, but recent studies indicate that elevated haematocrit and fibrinogen function may be of importance.The aim of this study was to characterise the haemostatic profile and examine the potential role of haematocrit on clot formation and strength in CCHD patients. Furthermore to examine whether CCHD patients with history of haemoptysis have diminished fibrinogen function compared to those without haemoptysis.

Methods

In a prospective study 75 adult CCHD patients had haematocrit, platelet count, and plasma fibrinogen concentration examined. Furthermore thrombelastography(TEG) as well as TEG Functional Fibrinogen(TEG FF) assay evaluating fibrinogen function(FLEV) was performed. Data were compared with historical data regarding previous haemoptysis in CCHD patients.

Results

Haematocrit was 57 ± 8% and platelet counts in the lower normal range. TEG revealed a hypocoagulable condition with impaired clot formation. TEG values were correlated to haematocrit, indicating that elevated haematocrit causes impaired clot formation and strength. Despite high levels of plasma fibrinogen, TEG FF demonstrated that FLEV was diminished and negatively correlated to haematocrit. Furthermore CCHD patients with previous history of haemoptysis had significantly lower FLEV compared to CCHD patients without haemoptysis.

Conclusion

Patients with CCHD are hypocoagulable mainly due to impaired fibrinogen function. Despite a low platelet count, platelet function does not seem to be severely affected in CCHD patients. Haemostasis, and especially fibrinogen function, is negatively affected by elevated haematocrit, and fibrinogen function is diminished in CCHD patients with haemoptysis.     

Partial splenic embolization for hypersplenism in cirrhosis: A long-term outcome in 62 patients

BackgroundAlthough partial splenic embolization (PSE) has been widely used for treatment of leucocytopaenia and thrombocytopaenia in cirrhosis, only few studies on the correlation between splenic infarction rate and long-term outcome of partial splenic embolization have been reported so far.AimTo evaluate long-term results of partial splenic embolization with different infarction rates in cirrhotic patients with hypersplenism.MethodsSixty-two consecutive patients with hypersplenism in cirrhosis received partial splenic embolization. According to the splenic infarction rate after partial splenic embolization, the patients were divided into three groups: more than 70% in group A (n = 12), 50–70% in group B (n = 34), and less than 50% in group C (n = 16). The post-partial splenic embolization following-up time was 5 years.ResultsBefore partial splenic embolization, there were no significant differences among the three groups with respect to sex, age, splenic volume, Child-Pugh class, oesophageal varices, and peripheral blood cell counts. After partial splenic embolization, the short- and long-term outcomes of leucocyte and platelet counts showed significant difference among the three groups (P < 0.001). In groups A and B, the leucocyte and platelet counts after partial splenic embolization remained significantly higher than those before partial splenic embolization for 2 weeks to 5 years (P < 0.05), the post-partial splenic embolization leucocyte and platelet counts was even higher in group A than in group B; while in group C, leucocyte and platelet count improvement only lasted for 6 months after partial splenic embolization. No significant changes were observed concerning blood red cell counts and liver function parameters after partial splenic embolization among the three groups. Severe complications occurred in six patients (50%) in group A and three patients (8.8%) in group B (P < 0.05), while in group C, no severe complications developed.ConclusionsIn partial splenic embolization, the splenic infarction rate should be limited to 50%–70% in order to ensure the long-term efficacy in alleviating hypersplenism and reduce complications.     

Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals

IntroductionThe aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents.Patients and methodsThis cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness–spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed.ResultsNinety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p = 0.02), spleen stiffness measurement (39.4 vs 46.05; p = 0.04), liver stiffness–spleen diameter to platelet ratio score (1.21 vs 2.02; p = 0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p = 0.04) and variceal risk index (?3.4 vs ?1.02; p = 0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3 kPa for liver stiffness measurement and 27 kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance.DiscussionLiver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.     

HEPACONTROL. A program that reduces early readmissions,mortality at 60 days,and healthcare costs in decompensated cirrhosis

Background & aimsDecompensated cirrhosis patients have an elevated incidence of early readmission, mortality and economic burden. The aims of HEPACONTROL were to reduce early readmission and to evaluate its impact on mortality and emergency department visits.Patients and methodsQuasi-experimental study with control group which compared two cohorts of patients discharged after being admitted for cirrhosis-related complications. A prospective cohort (n = 80), who followed the HEPACONTROL program, which began with a follow-up examination seven days after discharge at the Hepatology Unit Day Hospital and a retrospective cohort of patients (n = 112), who had been given a standard follow-up. Outcome variables that were compared between both groups were early readmission rates, the number of emergency department visits post-discharge, financial costs and mortality.ResultsThe rate of early readmission was lower in the group with HEPACONTROL (11.3% vs 29.5%; P = .003). Also, the mean number of visits to the emergency department post-discharge (1.10 ± 1.64 vs 1.71 ± 2.36; P = .035), mortality at 60 days (3.8% vs 14.3%; P = .016), and the cost of early readmission were all lower compared with the group with standard follow-up (P = .029).ConclusionsHEPACONTROL decreases the incidence of early readmission the rate of emergency department visits and mortality at 60 days in patients with decompensated cirrhosis, and it is cost-effective.     

On the association between circulating biomarkers and atherosclerotic calcification in a cohort of arterial disease participants

Background and aimsAtherosclerotic calcification is a powerful predictor of cardiovascular disease. This study aims to determine whether circulating levels of a local/systemic calcification inhibitor or a marker of bone formation correlate with measures of coronary or extracoronary calcification.Methods and resultsClinical computed tomography (CT) was performed on 64 arterial disease participants undergoing carotid and lower extremity endarterectomy. Coronary artery calcium (CAC) scores and volumes were acquired from the CT scans (n = 42). CAC scores and volumes were used to derive CAC density scores. Micro-CT was performed on excised carotid (n = 36) and lower extremity (n = 31) plaques to quantify the volume and volume fraction of extracoronary calcification. Circulating levels of dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP), fetuin-A, carboxylated and uncarboxylated osteocalcin (ucOC) were quantified using commercial immunoassays. Carotid participant CAC density scores were moderately negatively correlated with plasma dp-ucMGP (r_s = ?0.592, P = 0.008). A weak negative association was found between CAC scores and %ucOC for all participants (r_s = ?0.335, P = 0.040). Another weak negative correlation was observed between fetuin-A and the volume of calcification within excised carotid specimens (r_s = ?0.366, P = 0.031). Despite substantial differences in coronary and extracoronary calcium measurements, the levels of circulating biomarkers did not vary significantly between carotid and lower extremity subgroups.ConclusionCorrelations identified between circulating biomarkers and measures of coronary and extracoronary calcium were not consistent among participant subgroups. Further research is required to determine the association between circulating biomarkers, coronary and extracoronary calcium.     

Dual Antiplatelet Therapy Discontinuation,Platelet Reactivity,and Adverse Outcomes After Successful Percutaneous Coronary Intervention

ObjectivesThe purpose of this study was to assess the extent to which the association between premature dual antiplatelet therapy (DAPT) discontinuation and excess risk of thrombotic events varies according to the reason and timing of DAPT discontinuation and whether high on-treatment platelet reactivity (HPR) influences the risk of thrombotic events after premature DAPT discontinuation.BackgroundDAPT after percutaneous coronary intervention (PCI) suppresses platelet reactivity, and HPR on clopidogrel after PCI is associated with an increased risk of thrombotic events.MethodsADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of 8,582 patients successfully treated with coronary drug-eluting stents that assessed HPR on clopidogrel. For patients who discontinued aspirin or clopidogrel at any time during the study, the reasons for discontinuation were systematically categorized.ResultsPlanned DAPT discontinuation occurred within 2 years in 3,203 (37.3%) patients. One thousand four hundred eighteen (16.5%) patients discontinued DAPT for unplanned reasons, including surgery or trauma (n = 768 [8.9%]), patient nonadherence (n = 321 [3.7%]), bleeding complications (n = 264 [3.1%]), and drug allergy or hypersensitivity (n = 113 [1.3%]). Unplanned but not planned DAPT discontinuation was associated with an increased risk of a major adverse cardiac event (MACE, defined as the composite of cardiac death, myocardial infarction, or stent thrombosis); with highest risk within 3 months after PCI (adjusted HR: 7.65, 95% CI: 2.77-21.10 vs adjusted HR: 2.47, 95% CI: 1.70-3.58 for unplanned DAPT discontinuation ≥3 months after PCI). MACE risk after DAPT discontinuation was not moderated by HPR (P_interaction = 0.91).ConclusionsIn this large-scale all-comers registry, premature DAPT discontinuation for unplanned reasons occurred in approximately 1 of 6 patients after DES implantation and was associated with a markedly increased risk of MACEs. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)     

More frequent olive oil intake is associated with reduced platelet activation in obesity

Background and aimsObesity is an independent risk factor for atherosclerotic cardiovascular disease (CVD), and platelet hyperactivation in obesity may contribute to this association. Olive oil consumption is associated with lower cardiovascular disease (CVD) risk in the general population. However, little is known for individuals with obesity. We investigated whether olive oil intake is associated with platelet activation in obesity.Methods and resultsWe assessed platelet activation (surface P-selectin expression) with and without thrombin exposure and diet composition in 63 patients with severe obesity.Among 63 subjects with obesity, the mean age was 32.2 ± 8.0 years and BMI 44.1 ± 8.5 kg/m². Olive oil intake was stratified into <1 time/week (n = 21), 1–3 times/week (n = 18), ≥4 times/week (n = 24). Strata did not differ by age, BMI or platelet count. Unstimulated P-selectin expression did not differ by olive oil consumption. Subjects with more frequent olive oil intake exhibited lower P-selectin expression on submaximal thrombin exposure.ConclusionsMore frequent olive oil intake is associated with reduced thrombin-induced platelet activation in obesity.     

Upregulation of CD40/CD40L system in rheumatic mitral stenosis with or without atrial fibrillation

Thrombelastography (TEG) analyses the status of blood coagulation including abnormalities associated with low platelet count. The aim of this study was to investigate the changes in TEG parameters in idiopathic thrombocytopenic purpura (ITP) patients. Thirty nine patients with ITP (platelet count?<?100?×?103 µl^?1) were included in the study. Age-matched 17 patients with thrombocytopenia due to chemotherapy were selected as a control group. Platelet count was positively correlated with maximum clot formation (MCF) in INTEM (r?=?0.716, p?<?0.001) and MCF in EXTEM (r?=?0.679, p?<?0.001); negatively correlated with clot formation time (CFT) in INTEM (r?=??0.755, p?<?0.001) and CFT in EXTEM (r?=??0.585, p?<?0.001) in ITP patients. Platelet count was positively correlated with MCF in INTEM (r?=?0.776, p?<?0.001) and MCF in EXTEM (r?=?0.878, p?<?0.001); negatively correlated with CFT in INTEM (r?=??0.627, p?<?0.001) in control group. Receiver operating characteristic curves to describe the critical platelet count and fibrinogen level that affect MCF revealed 31?×?103?µl^?1 and 375 mg?dl^?1 as cut-off values, respectively. In conclusion, ROTEM determines the contribution of fibrinogen and platelets to clot strength in patients with ITP. MCF appears to be the most important TEG parameter in predicting bleeding in ITP patients that makes TEG superior to other hemostatic tests.     

Treatment options for sclerosing angiomatoid nodular transformation of spleen

BackgroundTo summarise the clinical features of Sclerosing angiomatoid nodular transformation (SANT) of the spleen and to compare the efficacy of three different surgical treatments.MethodsWe performed a retrospective analysis of patients with SANT of spleen treated at our center from 2009 to 2018. We compared the efficacy and safety of three different types of surgical procedures. ANOVA and the chi-square test were used for statistical analysis.ResultsA total of 37 patients were included. Most (35/37; 94.6%) were asymptomatic. A number presented as obscure boundary lesions such that malignancy could not be excluded. Open splenectomy was performed for 12 patients, laparoscopic splenectomy for 12 patients and laparoscopic partial splenectomy for 13 patients. Operation time (P = 0.355), blood loss (P = 0.135), length of hospital stay after operation (P = 0.271) and postoperative complications (P = 0.502) were comparable between the three groups. Duration of drainage tube placement was significantly longer in laparoscopic partial splenectomy patients (P = 0.006). Peak platelet count after operation was significantly lower in laparoscopic partial splenectomy patients (P < 0.001).ConclusionLaparoscopic partial splenectomy appears to be a technically feasible and therapeutically effective approach for SANT.     

Baveno VI criteria as a prognostic factor for clinical complications in patients with compensated cirrhosis

BackgroundCombination of liver stiffness measurement and platelets count is a tool to safely rule out varices needing treatment (VNT) in patients with compensated advanced chronic liver disease (cACLD). Aims: to evaluate 4-year liver-related complications and survival in low-risk patients according to Baveno VI criteria.Methodswe conducted a monocentric retrospective analysis of prospectively collected data of all consecutive patients, with cirrhosis (LSM≥12.5 kPa) and without previous complication, evaluated between 2012 and 2015. Liver-related complications and survival were compared between 2 groups of patients: favourable (LSM< 20 kPa and platelet count>150.000/mm3) and unfavourable Baveno VI status patients (LSM ≥ 20 kPa or platelet count ≤150.000/mm3).Results455 patients with cACLD were analysed. Two hundred patients had favourable Baveno VI criteria, 3.6% with VNT. The 4-year probability of being free of acute decompensation was higher in low-risk patients (94.4 ± 1.8% vs. 85.7%±2.6%, p = 0.018). Unfavourable Baveno status was independently associated with acute decompensation. The probability of being free of HCC was significantly higher in low-risk patients (94.2 ± 1.8% vs. 87.6 ± 2.4%, p = 0.048). Liver-related mortality was not different between the 2 groups (p = 0.56).ConclusionThe Baveno VI criteria could predict clinical outcome in cACLD.     

Comparison of Interferon-α-based therapy and nucleos(t)ide analogs in preventing adverse outcomes in patients with chronic hepatitis B

BackgroundWhether interferon (IFN)-α therapy is better than nucleos(t)ide analogs (NAs) in the prevention of adverse outcomes, including hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is still uncertain or controversial. This study aimed to compare the cumulative incidence of adverse outcomes in patients with CHB on IFN-α- and NA-based therapies.MethodsThis was a retrospective study of patients with CHB on antivirals. Patients treated with IFN-α (IFN-α or peginterferon-α) with or without NAs were defined as the IFN-α group, and those only receiving NAs were defined as the NAs group. Propensity score matching (PSM) was used to minimize baseline bias. Cox regression models were performed to select possible factors related to adverse outcomes development.ResultsAll 1247 patients were divided into the IFN-α (n = 877) and NAs (n = 370) groups. 26patients (20 and 6 in the NAs and IFN-α groups) developed adverse outcomes (decompensated cirrhosis, liver failure, HCC, liver transplantation and deaths) during a median follow-up of 5.2 years. The cumulative adverse outcomes occurrence at 10 years was significantly lower in the IFN-α group than in the NAs group in all (1.1% vs. 11.9%, P <0.001) and treatment-naïve (1.1% vs. 12.4%, P <0.001) patients. Similar trends were observed after PSM and differentiation of cirrhosis. Multivariate analysis before and after PSM showed that IFN-α-based treatment was independently associated with a lower adverse outcomes incidence (before/after PSM: P = 0.001/P = 0.002). HCC risk stratification analyses revealed that the superiority of IFN-α in preventing HCC was more significant in patients with high-risk HCC.ConclusionsIFN-α-based therapy was superior to NAs in preventing adverse outcomes in patients with CHB regardless of cirrhosis, and in reducing HCC in those with a high risk of HCC.     

Hepatectomy for hepatocellular carcinoma larger than 10 cm: preoperative risk stratification to prevent futile surgery

ObjectivesAppropriate patient selection is important to achieving good outcomes and obviating futile surgery in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). The aim of this study was to identify independent predictors of futile outcomes, defined as death within 3 months of surgery or within 1 year from early recurrence following hepatectomy for huge HCC.MethodsThe outcomes of 149 patients with huge HCCs who underwent resection during 1995–2012 were analysed. Multivariate logistic regression analysis was performed to identify preoperative independent predictors of futility.ResultsIndependent predictors of 3‐month mortality (18.1%) were: total bilirubin level >34 μmol/l [P = 0.0443; odds ratio (OR) 16.470]; platelet count of <150 000 cells/ml (P = 0.0098; OR 5.039), and the presence of portal vein tumour thrombosis (P = 0.0041; OR 5.138). The last of these was the sole independent predictor of 1‐year recurrence‐related mortality (17.2%). Rates of recurrence‐related mortality at 3 months and 1 year were, respectively, 6.3% and 7.1% in patients with Barcelona Clinic Liver Cancer (BCLC) stage A disease, 12.5% and 14% in patients with BCLC stage B disease, and 37.8% (P = 0.0002) and 75% (P = 0.0002) in patients with BCLC stage C disease.ConclusionsAccording to the present data, among patients submitted to hepatectomy for huge HCC, those with a high bilirubin level, low platelet count and portal vein thrombosis are at higher risk for futile surgery. The presence of portal vein tumour thrombosis should be regarded as a relative contraindication to surgery.