Prophylaxis Of Bleeding Research Articles

Considerations in the development of the International Multicenter Pediatric Portal Hypertension Registry

AbstractPortal hypertension, a common sequela of chronic liver disease, is complicated by variceal hemorrhage, one of its most serious complications. Evidence‐based approaches to managing variceal hemorrhage are limited by the scarcity of data related to this rare entity. Multicenter international registries are increasingly utilized to garner critical information about rare diseases. The International Multicenter Pediatric Portal Hypertension Registry (IMPPHR) was developed to acquire pediatric data about the mortality of first variceal hemorrhage and approaches to primary and second prophylaxis of variceal hemorrhage with a goal of improving outcomes in children with portal hypertension. IMPPHR evolved from pediatric portal hypertension symposia at the Baveno V and VI meetings in 2010 and 2015, with a formal executive committee initiating the development of IMPPHR in 2019. The registry opened in 2020, with data closure in 2024, including information from 44 centers and >700 subjects. The complexities and approaches to developing IMPPHR are described.

Portal Hypertensive Gastropathy and MELD-Na Score Predict Recurrent Gastrointestinal Bleeding After TIPSS: An ALTA Group Study.

Transjugular intrahepatic portosystemic shunt (TIPSS) is highly effective for treatment of variceal bleeding; however, factors contributing to rebleeding complications remain unclear. In this study, we aim to determine risk factors for recurrent portal hypertensive gastrointestinal bleeding following TIPSS. Utilising the Advancing Liver Therapeutic Approaches multicentre database, we retrospectively identified adult patients who underwent TIPSS for secondary prophylaxis of variceal bleeding and had a gastrointestinal rebleeding event within 1 year. We developed multivariable logistic regression models to identify clinical/procedural characteristics associated with rebleeding. We identified 476 patients, predominately middle-aged (mean age 57), male (62%) and White (65%), with mean MELD-Na 16. 16% (n = 77) had a rebleeding event; these patients were more likely to be male (p = 0.016), with higher serum creatinine (p = 0.005), MELD-Na (p = 0.0002), portal hypertensive gastropathy on pre-TIPSS upper endoscopy (p = 0.000) and with higher incidence of TIPSS revision (p = 0.000). There were no significant differences in type of TIPSS endoprosthesis, concurrent embolotherapy, and post-TIPSS pressure gradients between those who experienced rebleeding and those who did not. After adjusting for TIPSS revision, multivariable analysis revealed MELD-Na and presence of portal hypertensive gastropathy on pre-TIPSS endoscopy were independently associated with rebleeding. In this retrospective analysis of a multicentre, nationally representative database, we found that apart from TIPSS-related factors, high MELD-Na and portal hypertensive gastropathy on pre-TIPSS endoscopy were independent predictors of rebleeding within 1 year following TIPSS. These variables may be used to identify high-risk patients who may require additional monitoring following TIPSS.

Combination of carvedilol with variceal band ligation in prevention of first variceal bleed in Child-Turcotte-Pugh B and C cirrhosis with high-risk oesophageal varices: the ‘CAVARLY TRIAL’

ObjectivesBeta-blockers and endoscopic variceal band ligation (VBL) have been preferred therapies for primary prophylaxis of variceal bleeding. However, the choice of therapy in patients with advanced liver disease with high-risk...

Efficacy and safety of Ilaprazole for stress ulcer - associated upper gastrointestinal bleeding prophylaxis in critically ill patients: a randomized, double-blind, non-inferiority phase 3 trial

Efficacy and safety of Ilaprazole for stress ulcer - associated upper gastrointestinal bleeding prophylaxis in critically ill patients: a randomized, double-blind, non-inferiority phase 3 trial

Efficacy and safety of a recombinant von Willebrand factor treatment in acquired von Willebrand syndrome in case of bleeding and surgical procedures.

Acquired von Willebrand syndrome (AVWS) is a rare haemorrhagic disorder. The prophylaxis and treatment of bleeding before surgery are complex. Since 2018, a new recombinant VWF (rVWF) concentrate that contains no factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France. To describe the real-world experience of using rVWF in non-surgical bleeding and surgical procedures in patients with AVWS. Fifteen bleeding episodes in seven patients and 16 surgeries in 10 patients were retrospectively analysed in t French haemostasis centres. During bleeding, the median number of infusions was only 1 (range 1-27) with a median loading dose of 58IU/kg (range 17-116) rVWF and a total median dose of 65IU/kg (range 35-1488) rVWF. Bleeding control was rated markedly effective in 73% (11/15) of the cases and ineffective in 27% (4/15). During surgeries, the median number of infusions was 3 (range 1-8) with a preoperative loading dose of 60IU/kg (range 23-118) rVWF and a total median dose of 123IU/kg (range 31-542). The overall clinical efficacy was qualified as excellent, good and poor (ISTH criteria) in respectively 7 (43%), 6 (38%) and 3 (19%) procedures. There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events nor adverse events were reported. This French 'real-world' experience shows that rVWF could be of interest in the treatment and prophylaxis of bleeding in patients with AVWS, with no clinically significant safety concern.

Platelet transfusion.

Platelet transfusions, used as prophylaxis or treatment for bleeding, are potentially life-saving. In many countries, demand for platelet transfusion is rising. Platelets are a limited and costly resource, and it is vital that they are used appropriately. This study will explore the evidence behind platelet transfusions in different contexts, in particular recent and important research in this area. Recent randomized clinical trials demonstrate the efficacy of platelet transfusions in some contexts but potential detrimental effects in others. Platelet transfusions also carry risk of transfusion reactions, bacterial contamination and platelet transfusion refractoriness. Observational and clinical studies, which highlight approaches to mitigate these risks, will be discussed. There is growing interest in cold-stored or cryopreserved platelet units, which may improve platelet function and availability. Clinical trials also highlight the efficacy of other supportive measures such as tranexamic acid or thrombopoietin receptor agonists in patients with bleeding. Although platelet transfusions are beneficial in many patients, there remain many settings in which the optimal use of platelet transfusions is unclear, and some situations in which they may have detrimental effects. Future clinical trials are needed to determine optimal use of platelet transfusions in different patient populations.

Improved prevention of bleeding episodes with emicizumab in 3 patients with concomitant hemophilia A and von Willebrand disease.

The typical phenotype of hemophilia A (HA) is that of frequent bleeding episodes, up to several per month, unless prophylactic factor VIII (FVIII) replacement or alternatives are given. Related bleeding may be heightened in severity or frequency by co-morbid bleeding disorders. Based on the reported prevalence of von Willebrand disease (VWD) of up to 1% of the general population, the co-existence of HA and VWD occurs, but is likely less recognized. Prophylactic FVIII replacement may or may not adequately prevent bleeding in persons with HA and mild VWD, and plasma-derived concentrates containing FVIII and von Willebrand factor (VWF) may be used for more successful bleeding prophylaxis. However, therapy adherence remains problematic for many reasons, one being treatment via intravenous access. Emicizumab is a nonfactor subcutaneous prophylactic therapy for HA that may overcome this concern. We describe three patients, with severe HA and VWD, for whom regular FVIII/VWF prophylaxis was deemed inadequate. FVIII/VWF prophylaxis was replaced with weekly prophylactic injections of the bispecific monoclonal antibody, emicizumab. When the patients were transitioned to emicizumab, all experienced a significant reduction in their annualized bleed rate (ABR). Although the mechanism of action does not directly affect or replace VWF function, emicizumab may be an effective prophylaxis alternative to FVIII/VWF concentrate in patients with concomitant severe HA and VWD.

Nationwide survey analysis of esophagogastric varices in portal hypertension based on endoscopic management in China

AbstractAimsThe endoscopic treatment of esophagogastric varices is challenging, and the nationwide application of endoscopic therapies for various types of esophagogastric varices and different clinical scenarios remains unclear. This study investigated the use of endoscopic therapy for portal hypertension in China.MethodsThis study used a questionnaire survey initiated by the Liver Health Consortium in China to investigate the use of endoscopic therapies for portal hypertension. Questionnaires were released online from January 30, 2023 to February 28, 2023 and filled out by chief physicians or senior instructors responsible for endoscopic therapies in participating hospitals across 31 provinces (autonomous regions and municipalities) in China. Comparisons of guideline adherence between primary and referral medical centers were performed using the chi‐square test or Fisher's exact test.ResultsIn total, 836 hospitals participated in the survey. For primary and secondary prophylaxis of esophagogastric variceal bleeding (EGVB), adherence to the national guidelines was 72.5% (606/836) and 39.2% (328/836), respectively. Significant differences were observed in the rate of adherence between the primary and referral centers for primary (79.9% [111/139] vs. 71.0% [495/697], p = 0.033) and secondary prophylaxis (27.3% [38/139] vs. 41.6% [290/697], p = 0.002). Of the hospitals, 78.2% (654/836) preferred endoscopic therapies for acute EGVB, and the timing of endoscopy was usually within 12 h (48.5%, 317/654) and 12–24 h (36.9%, 241/654) after bleeding. Endoscopic therapy was more likely to be the first choice of treatment for acute EGVB in referral centers than in primary centers (82.6% [576/697] vs. 56.1% [78/139], p < 0.001). Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, the most prevalent procedures were cyanoacrylate injection combined with sclerotherapy (48.2% [403/836] and 29.9% [250/836], respectively); however, substantial hospitals preferred clip‐assisted therapies (12.4% [104/836] and 26.4% [221/836], respectively). Nonselective beta‐blockers were routinely used in 73.4% (614/836) of hospitals during the perioperative period of EGVB management, and propranolol (88.8%, 545/614) and carvedilol (37.5%, 230/614) were the most widely used nonselective beta‐blockers.ConclusionsThis survey clarified that various endoscopic procedures have been implemented nationwide in China. Participating hospitals have actively performed emergent endoscopy for acute EGVB; however, these hospitals do not adequately follow recommendations regarding primary and secondary prophylaxis of EGVB. In the future, standardizing the selection of endoscopic procedures and improving compliance with guidelines is crucial.

Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review.

Damoctocog alfa pegol (BAY 94-9027, Jivi®), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies. The PK of damoctocog alfa pegol was shown to be improved as compared with that of sucrose-formulated rFVIII (rFVIII-FS, Kogenate®), and was also demonstrated to be non-inferior to and, for some variables, more favorable than rFVIII-Fc fusion protein, efmoroctocog alfa (Elocta®; NCT03364998), rurioctocog alfa pegol (BAX 855, Adynovate®/Adynovi®; NCT04015492), and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, Advate®; NCT02483208). Damoctocog alfa pegol was generally well tolerated and none of the patients in any of the clinical trials, including the PROTECT VIII clinical program, HEM-POWR, or ongoing single-center studies, developed FVIII inhibitors. Efficacy for perioperative hemostasis has been demonstrated. Low bleeding rates were achieved across the studies, with twice weekly, every 5-day and every 7-day prophylaxis offering patients ≥ 12 years and their clinicians the chance to tailor treatment to individual needs and lifestyles, while maintaining long-term protection from bleeds and their consequences.

Association between preoperative proton pump inhibitor use and postoperative acute kidney injury in patients undergoing major surgery

Background Acute kidney injury (AKI) is a severe postoperative complication in patients undergoing major surgery. Proton pump inhibitors (PPIs) are used preoperatively as prophylaxis for postoperative gastrointestinal bleeding. Whether preoperative PPI use is associated with an increased risk of postoperative AKI remains uncertain. Methods This retrospective cohort study used electronic medical records from the clinical data warehouse of Peking University First Hospital to screen all adult hospitalizations undergoing major surgery between 1 January 2018 and 31 December 2020. Exposure was preoperative PPI use, defined as PPI use within 7 days before major surgery. The primary outcome was postoperative AKI, defined as AKI occurring within 7 days after major surgery; secondary outcomes included in-hospital AKI and in-hospital mortality. Results A total of 21,533 patients were included in the study (mean [SD] age, 57.8 [15.0] years; 51.2% male), of which 944 (4.4%) were prescribed PPI within 7 days before major surgery (PPI users). Overall, 72 PPI users (7.6%) and 356 non-users (1.7%) developed postoperative AKI. After adjustment, preoperative PPI use was associated with an increased risk of postoperative AKI (adjusted OR, 1.47; 95% CI, 1.04–2.07) and in-hospital AKI (adjusted OR, 1.41; 95% CI, 1.03–1.94). Moreover, subgroup analyses showed that the risk of PPI on postoperative AKI was amplified by the concomitant use of non-steroidal anti-inflammatory drugs or diuretics. No significant difference was observed between preoperative PPI use and in-hospital mortality in the fully adjusted model (adjusted OR 1.63; 95% CI, 0.55–4.85). Conclusions Preoperative PPI use was associated with an increased risk of AKI in patients undergoing major surgery. This risk may be enhanced by the concomitant use of other nephrotoxic drugs. Clinicians should weigh the pros and cons before initiating PPI prophylaxis.

Emicizumab in Type 3 von Willebrand Disease: Report of a Case with an Alloantibody and Literature Review

AbstractType 3 von Willebrand disease (VWD), the most severe form of VWD, is an inherited recessive bleeding disorder caused by the complete deficiency of von Willebrand factor (VWF). The reported prevalence is 1 per million but varies worldwide according to the frequency of consanguineous marriages. The clinical phenotype is characterized not only by mucocutaneous bleedings, but also by hemarthroses and muscle hematoma, as in patients with moderate hemophilia. Long-term prophylaxis with factor (F)VIII/VWF concentrates is recommended in patients with a history of severe and frequent bleeds. A rare complication of replacement therapy is the development of alloantibodies against VWF, with the consequences of an ineffective therapy and risk of anaphylactic reactions upon treatment. Emicizumab is the first bispecific monoclonal antibody that mimics FVIII coagulant activity and is approved for prophylaxis of bleeding in patients with inherited hemophilia A with or without inhibitors and recently also for acquired hemophilia. In this manuscript we report and discuss available data in the literature on the use of emicizumab in type 3 VWD and describe the case of a female patient with type 3 VWD with a history of alloantibodies against VWF and posttransfusion anaphylaxis, recently and successfully put on off-label prophylaxis with emicizumab.

Association between Complications and Death within 30 days after General Surgery

Objective: To determine the epidemiology of post-operative complications among general surgery patients, inform their relationships with 30-day mortality, and determine the attributable fraction of death of each postoperative complication. Background: The contemporary causes of post-operative mortality among general surgery patients are not well characterized. Methods: VISION is a prospective cohort study of adult non-cardiac surgery patients across 28 centres in 14 countries, who were followed for 30 days after surgery. For the subset of general surgery patients, a cox proportional hazards model was used to determine associations between various surgical complications and post-operative mortality. The analyses were adjusted for preoperative and surgical variables. Results were reported in adjusted hazard ratios (HR) with 95% confidence intervals (CI). Results: Among 7950 patients included in the study, 240 (3.0%) patients died within 30 days of surgery. Five post-operative complications (myocardial injury after non-cardiac surgery [MINS], major bleeding, sepsis, stroke, and acute kidney injury resulting in dialysis) were independently associated with death. Complications associated with the largest attributable fraction (AF) of post-operative mortality (i.e., percentage of deaths in the cohort that can be attributed to each complication, if causality were established) were major bleeding (n=1454, 18.3%, HR 2.49 95%CI 1.87-3.33, P<0.001, AF 21.2%), sepsis (n=783, 9.9%, HR 6.52, 95%CI 4.72-9.01, P<0.001, AF 15.6%), and MINS (n=980, 12.3%, HR 2.00, 95%CI 1.50-2.67, P<0.001, AF 14.4%). Conclusion: The complications most associated with 30-day mortality following general surgery are major bleeding, sepsis, and MINS. These findings may guide the development of mitigating strategies, including prophylaxis for perioperative bleeding.

Indications and outcomes of transjugular intrahepatic portosystemic shunt insertion in two regional Australian hepatology centres.

Transjugular intrahepatic portosystemic shunt (TIPS) is an important therapy for complications of portal hypertension but remains underutilised in regional settings. The aim of this study is to explore the demographics, indications, outcomes and complications in patients undergoing TIPS in two regional hepatology centres. Retrospective analysis was undertaken of all patients undergoing TIPS at two regional centres between January 2017 and March 2023. The primary outcome measures were efficacy and complications of TIPS. Patient demographics (such as age, baseline liver severity scores and aetiology of liver disease) and indications for TIPS are detailed. Forty-eight patients underwent TIPS. Median age was 56 years (interquartile range (IQR): 46-65). The most common indications for TIPS were refractory ascites (n = 17) and failure of secondary prophylaxis of variceal bleeding (n = 13). Cumulative survival at 3 months and 1 year was 93% and 77% respectively. There was no significant difference in outcomes based on TIPS indication. The median number of paracenteses in patients undergoing TIPS for refractory ascites 1 year pre- and post-TIPS were 10 (IQR: 4.5-16) and 2 (IQR: 0-4) respectively (P < 0.001). There were no procedure-related deaths. Inpatient management of liver disease complications had a mean cost of $32 874.67 (SEM: 7779) in 1 year pre-TIPS compared with $12 304.70 (SEM: 3531.1) in 1 year post-TIPS (P < 0.001). TIPS is a safe and effective treatment to reduce complications of portal hypertension and can be performed successfully in the regional setting.

Estimating the cost of Rh testing and prophylaxis in early pregnancy: A time-driven activity-based costing study

ObjectiveTo estimate the cost of Rhesus (Rh) testing and prophylaxis for first-trimester vaginal bleeding in the ambulatory setting. Study designWe used time-driven, activity-based costing to analyze tasks associated with Rh testing and prophylaxis of first-trimester vaginal bleeding at one hospital-based outpatient and two independent reproductive health clinics. At each site, we observed 10 patients undergoing Rh-typing and two patients undergoing Rh prophylaxis. We computed the costs of blood Rh-typing by both fingerstick and phlebotomy, cost of locating previous blood type in the electronic health record (available for 69.8% of hospital-based patients), and costs associated with Rh immune globulin prophylaxis. All costs are reported in 2021 US dollars. ResultsThe hospital-based clinic reviewed the electronic health record to confirm Rh-status (cost, $26.18 per patient) and performed a phlebotomy, at $47.11 per patient, if none was recorded. The independent clinics typed blood by fingerstick, at a per-patient cost of $4.07. Rh-immune globulin administration costs, including the medication, were similar across facilities, at a mean of $145.66 per patient. Projected yearly costs for testing and prophylaxis were $55,831 for the hospital-based clinic, which was the lowest-volume site, $47,941 for Clinic A, which saw 150 patients/month, and $185,654 for Clinic B, which saw 600 patients/month. ConclusionsRh testing and prophylaxis for first-trimester vaginal bleeding generates considerable costs for outpatient facilities, even for Rh-positive patients with a prior blood type on record. ImplicationsRh testing and prophylaxis for first-trimester bleeding generate considerable costs even for Rh-positive patients and those with a previously known blood type. These findings highlight the need to reconsider this practice, which is no longer supported by evidence and already safely waived in multiple medical settings in the United States and around the world.

Improvement of quality of care provided to outpatients with hepatic cirrhosis after an educational intervention.

A set of indicators has been reported to measure the quality of care for cirrhotic patients, and previously published studies report variable adherence rates to these indicators. This study aimed to assess the quality of care provided to cirrhotic outpatients before and after an educational intervention by determining its impact on adherence to quality indicators. We conducted a quasi-experimental, cross-sectional study including 324 cirrhotic patients seen in 2017 and 2019 at a tertiary teaching hospital in Spain. Quality indicators were assessed in five domains: documentation of cirrhosis etiology, disease severity assessment, hepatocellular carcinoma (HCC) screening, variceal bleeding prophylaxis, and vaccination. After identifying areas for improvement, an educational intervention was implemented. A second evaluation was performed after the intervention to assess changes in adherence rates. Before the intervention, adherence rates were excellent (>90%) for indicators related to variceal bleeding prophylaxis and documentation of cirrhosis etiology, acceptable (60-80%) for HCC screening and disease severity assessment, and poor (<50%) for vaccinations. After the educational intervention, there was a statistically significant improvement in adherence rates for eight indicators related to HCC screening (70-90%), disease severity assessment (90%), variceal bleeding prophylaxis (>90%), and vaccinations (60-90%). Our study demonstrates a significant improvement in the quality of care provided to cirrhotic outpatients after an educational intervention. The findings highlight the importance of targeted educational interventions to enhance adherence to quality indicators in the management of cirrhosis.

Azygoportal disconnection or a combination of non-selective beta-blockers and endoscopic variceal ligation to prevent recurrent bleeding in patients with cirrhosis awaiting transplantation

Objective: to compare the efficacy of azygoportal disconnection (APD) surgery and a combination between endoscopic variceal ligation (EVL) and non-selective beta-blockers (NSBBs) in the prevention of recurrent variceal bleeding (RVB). To compare the incidence of gastric variceal bleeding (GVB) after these manipulations in patients with decompensated cirrhosis waitlisted for liver transplantation (LTx).Materials and methods. Patients with decompensated cirrhosis underwent RVB prophylaxis by APD surgery or by a combination of EVL and NSBBs.Results. There were no significant differences in clinical, laboratory, demographic parameters, MELD-Na and Child–Turcotte–Pugh (CTP) scores, and frequencies of medium- and large-sized varicose veins among subgroups of patients with different RVB prophylaxis methods Patients with decompensated cirrhosis who underwent APD surgery did not experience any RVB episodes during the LTx waiting period, which lasted two years from the start of bleeding prophylaxis. In the same period, RVB occurred in 100% of cases in the EVL plus NSBBs group. Using the Kaplan–Meier method with the Log-Rank test, a significant difference (p = 0.0001) was found between the proportions of non-RVB patients in the APD and EVL + NSBBs groups. In the meantime, 48.1% of patients who had APD surgery developed GVB, while 100% of cases in EVL + NSBBs group did not. The Kaplan–Meier method with the Log-Rank test revealed a significant difference (p = 0.0001) between the proportion of non-GVB patients in EVL + NSBBs and APD groups.

Proton pump inhibitors for gastrointestinal bleeding prophylaxis in critically ill patients: A systematic review protocol.

Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for preventing upper gastrointestinal bleeding in critically ill patients. However, concerns have arisen about the possible harms of using PPIs, including potentially increased risk of pneumonia, Clostridioides difficile infection, and more seriously, an increased risk of death in the most severely ill patients. Triggered by the REVISE trial, which is a forthcoming large randomized trial comparing pantoprazole to placebo in invasively mechanically ventilated patients, we will conduct this systematic review to evaluate the efficacy and safety of PPIs versus no prophylaxis for critically ill patients. We will systematically search randomized trials that compared gastrointestinal bleeding prophylaxis with PPIs versus placebo or no prophylaxis in adults in the intensive care unit (ICU). Pairs of reviewers will independently screen the literature, and for those eligible trials, extract data and assess risk of bias. We will perform meta-analyses using a random-effects model, and calculate relative risks for dichotomous outcomes and mean differences for continuous outcomes, and the associated 95% confidence intervals. We will conduct subgroup analysis to explore whether the impact of PPIs on mortality differs in more and less severely ill patients. We will assess certainty of evidence using the GRADE approach. This systematic review will provide the most up-to-date evidence regarding the merits and limitations of stress ulcer prophylaxis with PPIs in critically ill patients in contemporary practice.

Management of Portal Hypertension in Patients with Hepatocellular Carcinoma on Systemic Treatment: Current Evidence and Future Perspectives.

The management of CSPH in patients undergoing systemic treatment for HCC has emerged as a critical concern due to the absence of reliable diagnostic criteria and uncertainties surrounding therapeutic approaches. This review aims to underscore the primary pathophysiological aspects linking HCC and PH, while also addressing the current and emerging clinical strategies for the management of portal hypertension. A review of studies from January 2003 to June 2023 was conducted using the PubMed database and employing MeSH terms, such as "hepatocellular carcinoma", "immune checkpoint inhibitors", "systemic therapy", "portal hypertension", "variceal bleeding" and "tyrosine kinase inhibitors". Despite promising results of tyrosine kinase inhibitors in animal models for PH and fibrosis, only Sorafenib has demonstrated similar effects in human studies, whereas Lenvatinib appears to promote PH development. The impact of Atezolizumab/Bevacizumab on PH remains uncertain, with an increasing risk of bleeding related to Bevacizumab in patients with prior variceal hemorrhage. Given the absence of specific guidelines, endoscopic surveillance during treatment is advisable, and primary and secondary prophylaxis of variceal bleeding should adhere to the Baveno VII recommendations. Furthermore, in patients with advanced HCC, refinement of diagnostic criteria for CSPH and guidelines for its surveillance are warranted.

The Effectiveness of Prophylactic Epinephrine Compared to No Prophylaxis for Postpolypectomy Bleeding in Endoscopic Colorectal Surgery: A Systematic Review and Meta-Analysis.

Colorectal cancer prevention has seen significant advancements with colonoscopic polypectomy, a critical technique in clinical practice. However, postpolypectomy bleeding (PPB), particularly in the resection of large pedunculated polyps, remains a major complication. This systematic review and meta-analysis investigates the efficacy of prophylactic epinephrine injections in preventing PPB, addressing inconsistencies in the literature regarding its effectiveness. Employing a comprehensive search strategy, we rigorously selected studies for inclusion, focusing on those comparing prophylactic epinephrine with no intervention. The risk of bias was assessed using the Cochrane Risk of Bias assessment tool, ensuring a robust and reliable analysis. Our findings, based on an analysis of four studies involving 1,062 patients, indicate a significant reduction in early PPB with epinephrine use, with a marked decrease in bleeding incidence compared to the no-prophylaxis group. However, the impact on delayed bleeding was less conclusive, suggesting the need for further research in this area. Our study thus highlights the effectiveness of epinephrine as a preventive tool in colonoscopic polypectomywhile underscoring the complexity of bleeding risks and the necessity for ongoing investigation in optimizing patient outcomes.

Real-world long-term safety and effectiveness of turoctocog alfa in the treatment of haemophilia A in Japan: results from a multicentre, non-interventional, post-marketing study

ABSTRACT Objectives To assess the safety and effectiveness of turoctocog alfa in previously treated patients (PTPs) and previously untreated patients (PUPs) with haemophilia A in a real-world setting in Japan. Methods This multicentre, non-interventional, post-marketing study recruited patients with haemophilia A who initiated treatment with turoctocog alfa from 18 sites (08/2014-12/2018). The primary endpoint was adverse events (AEs) during the 2-year study period. Results The safety and effectiveness analysis set included 39 patients. In total, 13 (33.3%) patients reported ≥1 AE; incidence rate was 60.4 events/100 patient-years of exposure (PYE). Treatment was withdrawn in two cases: pruritus in a PTP and factor VIII inhibitor development in a PUP. Inhibitor development occurred in 2.6% of all patients, with an incidence rate of 3.8 events/100 PYE. The rate of inhibitor development was 0%, 25% and 20% in PTPs, PUPs and PUPs with severe type, respectively. The haemostatic success rate was 91.4% for 383 bleeding episodes and 85.7% for 14 surgeries. The negative binomial annualised bleeding rate for the prophylaxis regimen was 6.19 episodes/year (95% CI, 3.69–10.38). The mean (SD) total consumption of turoctocog alfa (n = 34; excluding FVIII inhibitors) was 5,382.6 (7,180.1) IU/kg/year/patient; consumption was 4,133.1 (1,452.4) IU/kg/year/patient for prophylaxis. Discussion The effectiveness and safety profiles were comparable to those observed in other turoctocog alfa trials; effectiveness analysis and consumption were not affected by treatment regimens. Conclusion Long-term use of turoctocog alfa therapy in clinical practice posed no newly identified safety issues and was effective for prophylaxis and treatment of bleeds in patients with haemophilia A in Japan.