Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders: from molecular mechanisms to clinical implications.

Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality. Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders, which may promote the development and progression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries. Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases. In this review, we emphasized the importance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations, epidemiology, and aberrant cellular composition involving the biliary ductules, cholangiocytes, immune system, fibroblasts, and the microbiome. We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies. This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.

Development of a Selective Aortic Arch Perfusion System in a Porcine Model of Exsanguination Cardiac Arrest.

Hemorrhage constitutes the majority of potentially preventable deaths from trauma. There is growing interest in endovascular resuscitation techniques such as selective aortic arch perfusion (SAAP) for patients in cardiac arrest. This involves active perfusion of the coronary circulation via a thoracic aortic balloon catheter and is approaching clinical application. However, the technique is complex and requires refinement in animal models before human use can be considered. This paper describes a large animal model of exsanguination cardiac arrest treated with a bespoke SAAP system. Swine were anesthetized, instrumented and a splenectomy was performed before a controlled, logarithmic exsanguination was initiated. Animals were heparinized and the shed blood collected in a reservoir. Once cardiac arrest was observed, the blood was pumped through an extra-corporeal circuit into an oxygenator and then delivered through a 10 Fr balloon catheter placed in the thoracic aorta. This resulted in the return of a spontaneous circulation (ROSC) as demonstrated by ECG and aortic root pressure waveform. This model and accompanying SAAP system allow for standardized and reproducible recovery from exsanguination cardiac arrest.

Aneurysm Morphology Is a More Significant Predictor of Survival than Hardman's Index in Patients with Ruptured or Acutely Symptomatic Abdominal Aortic Aneurysms.

Scoring systems such as Hardman's index are used to predict outcomes and stratify patients with ruptured abdominal aortic aneurysm (RAAA) or acutely symptomatic abdominal aortic aneurysm (SAAA) to active treatment or palliation. Aneurysm morphology is not included in these scoring systems. The aim of this study was to assess whether aneurysm morphology was an independent predictor of survival. Consecutive patients admitted from January 2006 to March 2017 with emergency presentation and primary diagnosis of abdominal aortic aneurysm were identified. Patients were stratified by age, gender, mode of presentation (RAAA versus SAAA), Hardman's Index, aneurysm morphology (suitability for endovascular aneurysm repair [EVAR]), and the procedure performed (endovascular versus open). Multivariable logistic regression analysis was used to determine predictors of survival. A total of 346 patients were included (RAAA: 250, SAAA: 96). Median age of patients was 75 years (range: 44-96); 284 (79%) were men and 75 (21%) were women. Three hundred twenty-five patients underwent preoperative computed tomography (CT) scan of these 156 (48%) fulfilled conservative instructions for use (IFU) for EVAR and another 64 (20%) were within the liberal IFU for EVAR. Median Hardman Index was 1 (range 0-5). Age (odds ratio [OR]: 1.72 [95% confidence interval {CI}: 1.15-2.23] [P < 0.001]), mode of presentation [(OR: 2.05 (95% CI: 1.45-3.31) (P < 0.001)], and aneurysm morphology being within conservative IFU for EVAR [(OR: 1.61 (95% CI: 1.08-2.03) (P = 0.02)], modality of repair (open versus EVAR), (OR: 0.81 [95% CI: 0.67-0.92], [P < 0.001]) were independent predictors of survival. Hardman's index (OR: 0.86 [95% CI: 0.69-1.11], [P = 0.16]) and gender (OR: 1.15 [95% CI: 0.83-1.32], [P = 0.24]) were not. Aneurysm morphology is a significant predictor of survival after RAAA. This information should be included in any scoring system.

Do Integrated Systems of Stroke Care Improve Symptom to Surgery Times in Patients with Symptomatic Carotid Stenosis? A Single Centre Decision Tree Analysis.

OBJECTIVE: The objective of this study was to examine the impact of an integrated system of stroke care on symptom to surgery times, cost-effectiveness, and quality of life measures in patients with symptomatic carotid stenosis. METHODS: Patients who underwent carotid endarterectomy (CEA) in a regional vascular centre between April 1, 2011, and March 31, 2016, were identified from the National Vascular Registry (NVR). Risk of stroke on medical therapy for each patient was calculated using the Oxford stroke risk calculator. Symptom to surgery times were compared among patients referred from a stroke service providing an integrated stroke care and the stroke service in an adjacent NHS trust which provides standard urgent referral pathway. A decision analytic Markov process model was constructed to determine the cost-effectiveness of CEA versus medical treatment in patients who followed the standard and integrated pathways. This model examined the lifetime costs and health benefits of CEA through each pathway. RESULTS: A total of 376 patients underwent CEA, of whom 243 were managed through the integrated stroke pathway and 133 through the standard urgent referral pathway. Median symptom to surgery time was 11 (0-66) days for the former and 15 (3-90) days for the latter (p < .001). There was no significant difference in peri-operative stroke death rate between integrated (2.1%) and standard (1.5%) pathways (chi-square = 0.14, p = .73). CEA through the integrated pathway improved quality adjusted life expectancy by an additional 0.13 (0.64 QALYs [integrated pathway] to 0.51 QALYs [standard pathway]) and was associated with an incremental lifetime cost benefit of £2203.4. CONCLUSIONS: An integrated stroke system of care is cost-effective and associated with significant improvements in quality adjusted life years.

Once versus twice daily low molecular weight heparin for the initial treatment of venous thromboembolism.

BACKGROUND: In the initial treatment of venous thromboembolism (VTE) low molecular weight heparin (LMWH) is administered once or twice daily. A once daily treatment regimen is more convenient for the patient and may optimise home treatment. However, it is not clear whether a once daily treatment regimen is as safe and effective as a twice daily treatment regimen. This is the second update of a review first published in 2003. OBJECTIVES: To compare the efficacy and safety of once daily versus twice daily administration of LMWH. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2013) and CENTRAL (2013, Issue 4). SELECTION CRITERIA: Randomised clinical trials in which LMWH given once daily is compared with LMWH given twice daily for the initial treatment of VTE. DATA COLLECTION AND ANALYSIS: Two review authors assessed trials for inclusion and extracted data independently. MAIN RESULTS: Five studies were included with a total of 1508 participants. The pooled data showed no statistically significant difference in recurrent VTE between the two treatment regimens (OR 0.82, 0.49 to 1.39; P = 0.47). A comparison of major haemorrhagic events (OR 0.77, 0.40 to 1.45; P = 0.41), improvement of thrombus size (OR 1.41, 0.66 to 3.01; P = 0.38) and mortality (OR 1.14, 0.62 to 2.08; P = 0.68) also showed no statistically significant differences between the two treatment regimens. None of the five included studies reported data on post-thrombotic syndrome. AUTHORS' CONCLUSIONS: Once daily treatment with LMWH is as effective and safe as twice daily treatment with LMWH.

Antiplatelet agents for intermittent claudication.

BACKGROUND: Peripheral arterial disease (PAD) is common and is a marker of systemic atherosclerosis. Patients with symptoms of intermittent claudication (IC) are at increased risk of cardiovascular events (myocardial infarction (MI) and stroke) and of both cardiovascular and all cause mortality. OBJECTIVES: To determine the effectiveness of antiplatelet agents in reducing mortality (all cause and cardiovascular) and cardiovascular events in patients with intermittent claudication. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases group searched their Specialised Register (last searched April 2011) and CENTRAL (2011, Issue 2) for publications on antiplatelet agents and IC. In addition reference lists of relevant articles were also searched. SELECTION CRITERIA: Double-blind randomised controlled trials comparing oral antiplatelet agents versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication were included. Patients with asymptomatic PAD (stage I Fontaine), stage III and IV Fontaine PAD, and those undergoing or awaiting endovascular or surgical intervention were excluded. DATA COLLECTION AND ANALYSIS: Data on methodological quality, participants, interventions and outcomes including all cause mortality, cardiovascular mortality, cardiovascular events, adverse events, pain free walking distance, need for revascularisation, limb amputation and ankle brachial pressure indices were collected. For each outcome, the pooled risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) was calculated. MAIN RESULTS: A total of 12 studies with a combined total of 12,168 patients were included in this review. Antiplatelet agents reduced all cause (RR 0.76, 95% CI 0.60 to 0.98) and cardiovascular mortality (RR 0.54, 95% CI 0.32 to 0.93) in patients with IC compared with placebo. A reduction in total cardiovascular events was not statistically significant (RR 0.80, 95% CI 0.63 to 1.01). Data from two trials (which tested clopidogrel and picotamide respectively against aspirin) showed a significantly lower risk of all cause mortality (RR 0.73, 95% CI 0.58 to 0.93) and cardiovascular events (RR 0.81, 95% CI 0.67 to 0.98) with antiplatelets other than aspirin compared with aspirin. Antiplatelet therapy was associated with a higher risk of adverse events, including gastrointestinal symptoms (dyspepsia) (RR 2.11, 95% CI 1.23 to 3.61) and adverse events leading to cessation of therapy (RR 2.05, 95% CI 1.53 to 2.75) compared with placebo; data on major bleeding (RR 1.73, 95% CI 0.51, 5.83) and on adverse events in trials of aspirin versus alternative antiplatelet were limited. Risk of limb deterioration leading to revascularisation was significantly reduced by antiplatelet treatment compared with placebo (RR 0.65, 95% CI 0.43 to 0.97). AUTHORS' CONCLUSIONS: Antiplatelet agents have a beneficial effect in reducing all cause mortality and fatal cardiovascular events in patients with IC. Treatment with antiplatelet agents in this patient group however is associated with an increase in adverse effects, including GI symptoms, and healthcare professionals and patients need to be aware of the potential harm as well as the benefit of therapy; more data are required on the effect of antiplatelets on major bleeding. Evidence on the effectiveness of aspirin versus either placebo or an alternative antiplatelet agent is lacking. Evidence for thienopyridine antiplatelet agents was particularly compelling and there is an urgent need for multicentre trials to compare the effects of aspirin against thienopyridines.

Intra-peritoneal prophylactic agents for preventing adhesions and adhesive intestinal obstruction after non-gynaecological abdominal surgery.

BACKGROUND: Intra-abdominal adhesions are common and challenge patients, surgeons and other healthcare providers. They are potentially preventable and several agents that act as barriers between adjacent peritoneal surfaces have been evaluated for prophylaxis. Efficacy, judged by systematic reviews, has only been undertaken in gynaecological surgery. OBJECTIVES: To determine efficacy and safety of peritoneal adhesion prophylaxis on incidence, distribution and adhesion-related intestinal obstruction after non-gynaecological surgery. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials, the Cochrane Colorectal Cancer Group specialised register, MEDLINE (1966-2008), and EMBASE (1971-2008) were searched. SELECTION CRITERIA: Blinded and non-blinded, randomised and quasi-randomised clinical trials were considered. DATA COLLECTION AND ANALYSIS: Two authors individually conducted the searches and assessed the quality of studies for inclusion which were analysed using the Revman Analyses software 5.0.0 provided by the Cochrane collaboration. Meta-analysis used a random effects model. MAIN RESULTS: Seven randomised trials were eligible; six compared hyaluronic acid/carboxymethyl membrane (HA/CMC) and one 0.5% ferric hyaluronate gel against controls.HA/CMC reduced the incidence of adhesions (OR 0.15 (95% CI: 0.05, 0.43); p=0.0005) with reduced extent (WMD -25.9% (95% CI: -40.56, -11.26); p=0.0005) and severity. There was no reduction of intestinal obstruction needing surgical intervention (odds ratio: 0.84 (95% CI: 0.24, 2.7) with comparable overall morbidity and mortality.The study of 0.5% ferric hyaluronate gel was prematurely terminated and no valid conclusions could be made but there was a higher incidence of overall morbidity (OR 5.04; 95% CI: 1.1, 22.9) and ileus (OR: 9.29; 95% CI: 1.57, 54.77; p=0.01). IMPLICATIONS FOR PRACTICE: There is evidence that the use of HA/CMC membrane reduces incidence, extent and severity of adhesions which may, theoretically, have implications in re-operative abdominal surgery. There is no evidence that the incidence of intestinal obstruction or need for operative intervention is reduced. HA/CMC appears to be safe but there may be a risk of leak when wrapped around an anastomoses. HA/CMC may be considered for intra-abdominal, adhesion prophylaxis at a surgeon's discretion and clinical context. IMPLICATIONS FOR RESEARCH: Further research is needed to explore the effectiveness of other agents in abdominal surgery in general. Synergism, using agents which target different aspects of adhesiogenesis, with exploration effectiveness in a wide range of emergency and elective surgery should be considered. Longer term outcomes of recurrent intestinal obstruction and chronic pain, identification of high risk groups of patients with evaluation of cost-effectiveness are required.