Microtubule specialization by +TIP networks: from mechanisms to functional implications.

To fulfill their actual cellular role, individual microtubules become functionally specialized through a broad range of mechanisms. The 'search and capture' model posits that microtubule dynamics and functions are specified by cellular targets that they capture (i.e., a posteriori), independently of the microtubule-organizing center (MTOC) they emerge from. However, work in budding yeast indicates that MTOCs may impart a functional identity to the microtubules they nucleate, a priori. Key effectors in this process are microtubule plus-end tracking proteins (+TIPs), which track microtubule tips to regulate their dynamics and facilitate their targeted interactions. In this review, we discuss potential mechanisms of a priori microtubule specialization, focusing on recent findings indicating that +TIP networks may undergo liquid biomolecular condensation in different cell types.

Kinetochore-microtubule attachment in human cells is regulated by the interaction of a conserved motif of Ska1 with EB1.

The kinetochore establishes the linkage between chromosomes and the spindle microtubule plus ends during mitosis. In vertebrates, the spindle-kinetochore-associated (Ska1,2,3) complex stabilizes kinetochore attachment with the microtubule plus ends, but how Ska is recruited to and stabilized at the kinetochore-microtubule interface is not understood. Here, our results show that interaction of Ska1 with the general microtubule plus end-associated protein EB1 through a conserved motif regulates Ska recruitment to kinetochores in human cells. Ska1 forms a stable complex with EB1 via interaction with the motif in its N-terminal disordered loop region. Disruption of this interaction either by deleting or mutating the motif disrupts Ska complex recruitment to kinetochores and induces chromosome alignment defects, but it does not affect Ska complex assembly. Atomic-force microscopy imaging revealed that Ska1 is anchored to the C-terminal region of the EB1 dimer through its loop and thereby promotes formation of extended structures. Furthermore, our NMR data showed that the Ska1 motif binds to the residues in EB1 that are the binding sites of other plus end targeting proteins that are recruited to microtubules by EB1 through a similar conserved motif. Collectively, our results demonstrate that EB1-mediated Ska1 recruitment onto the microtubule serves as a general mechanism for the formation of vertebrate kinetochore-microtubule attachments and metaphase chromosome alignment.

More is different: Reconstituting complexity in microtubule regulation.

Microtubules are dynamic cytoskeletal filaments that undergo stochastic switching between phases of polymerization and depolymerization-a behavior known as dynamic instability. Many important cellular processes, including cell motility, chromosome segregation, and intracellular transport, require complex spatiotemporal regulation of microtubule dynamics. This coordinated regulation is achieved through the interactions of numerous microtubule-associated proteins (MAPs) with microtubule ends and lattices. Here, we review the recent advances in our understanding of microtubule regulation, focusing on results arising from biochemical in vitro reconstitution approaches using purified multiprotein ensembles. We discuss how the combinatory effects of MAPs affect both the dynamics of individual microtubule ends, as well as the stability and turnover of the microtubule lattice. In addition, we highlight new results demonstrating the roles of protein condensates in microtubule regulation. Our overall intent is to showcase how lessons learned from reconstitution approaches help unravel the regulatory mechanisms at play in complex cellular environments.

Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving ß-blockers+ligation to prevent re-bleeding.

BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

Episodic overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt does not increase mortality in patients with cirrhosis.

BACKGROUND & AIMS: Overt hepatic encephalopathy (OHE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS) placement, given its high incidence and possibility of refractoriness to medical treatment. Nevertheless, the impact of post-TIPS OHE on mortality has not been investigated in a large population. METHODS: We designed a multicenter, non-inferiority, observational study to evaluate the mortality rate at 30 months in patients with and without OHE after TIPS. We analyzed a database of 614 patients who underwent TIPS in three Italian centers and estimated the cumulative incidence of OHE and mortality with competitive risk analyses, setting the non-inferiority limit at 0.12. RESULTS: During a median follow-up of 30 months (IQR 12-30), 293 patients developed at least one episode of OHE. Twenty-seven (9.2%) of them experienced recurrent/persistent OHE. Patients with OHE were older (64 [57-71] vs. 59 [50-67] years, p <0.001), had lower albumin (3.1 [2.8-3.5] vs. 3.25 [2.9-3.6] g/dl, p = 0.023), and had a higher prevalence of pre-TIPS OHE (15.4% vs. 9.0%, p = 0.023). Child-Pugh and MELD scores were similar. The 30-month difference in mortality between patients with and without post-TIPS OHE was 0.03 (95% CI -0.042 to 0.102). Multivariable analysis showed that age (subdistribution hazard ratio 1.04, 95% CI 1.02-1.05, p <0.001) and MELD score (subdistribution hazard ratio 1.09, 95% CI 1.05-1.13, p <0.001), but not post-TIPS OHE, were associated with a higher mortality rate. Similar results were obtained when patients undergoing TIPS for variceal re-bleeding prophylaxis (n = 356) or refractory ascites (n = 258) were analyzed separately. The proportion of patients with persistent OHE after TIPS was significantly higher in the group of patients who died. The robustness of these results was increased following propensity score matching. CONCLUSION: Episodic OHE after TIPS is not associated with mortality in patients undergoing TIPS, regardless of the indication. IMPACT AND IMPLICATIONS: Overt hepatic encephalopathy (OHE) is a common complication in patients with advanced liver disease and it is particularly frequent following transjugular intrahepatic portosystemic shunt (TIPS) placement. In patients with cirrhosis outside the setting of TIPS, the development of OHE negatively impacts survival, regardless of the severity of cirrhosis or the presence of acute-on-chronic liver failure. In this multicenter, non-inferiority, observational study we demonstrated that post-TIPS OHE does not increase the risk of mortality in patients undergoing TIPS, irrespective of the indication. This finding alleviates concerns regarding the weight of this complication after TIPS. Intensive research to improve patient selection and risk stratification remains crucial to enhance the quality of life of patients and caregivers and to avoid undermining the positive effects of TIPS on survival.

BnaC4.BOR2 mediates boron uptake and translocation in Brassica napus under boron deficiency.

Boron (B) is an essential microelement in plant growth and development. However, the molecular mechanisms underlying B uptake and translocation in Brassica napus are poorly understood. Herein, we identified a low-B (LB)-inducible gene, namely BnaC4.BOR2, with high transcriptional activity in root tips, stele cells, leaves, and floral organs. The green fluorescence protein labelled BnaC4.BOR2 protein was localised to the plasma membrane to demonstrate the B efflux activity in yeast and Arabidopsis. BnaC4.BOR2 knockout considerably reduced B concentration in the root and xylem sap, and altered B distribution in different organs at low B supply, exacerbating B sensitivity at the vegetative and reproductive stages. Additionally, the grafting experiment showed that BnaC4.BOR2 expression in the roots contributed more to B deficiency adaptability than that in the shoots. The pot experiments with LB-soil revealed B concentration in leaves and siliques of BnaC4.BOR2 mutants were markedly reduced, showing an obvious B-deficient phenotype of 'flowering without seed setting' and a considerable reduction in seed yield in B-deficient soil. Altogether, the findings of this study highlight the crucial role of BnaC4.BOR2 in B uptake and translocation during B. napus growth and seed yield under LB conditions.

A streamlined, automated workflow to screen and triage large numbers of baculoviruses for protein expression.

The baculovirus expression system is a powerful and widely used method to generate large quantities of recombinant protein. However, challenges exist in workflows utilizing either liquid baculovirus stocks or the Titerless Infected-Cells Preservation and Scale-Up (TIPS) method, including the time and effort to generate baculoviruses, screen for protein expression and store large numbers of baculovirus stocks. To mitigate these challenges, we have developed a streamlined, hybrid workflow which utilizes high titer liquid virus stocks for rapid plate-based protein expression screening, followed by a TIPS-based scale-up for larger protein production efforts. Additionally, we have automated each step in this screening workflow using a custom robotic system. With these process improvements, we have significantly reduced the time, effort and resources required to manage large baculovirus generation and expression screening campaigns.

French guidelines on TIPS: Indications and modalities.

Transjugular intrahepatic portosystemic shunt (TIPS) has become essential in the treatment or prevention of portal hypertension-related complications. In the early 1990s, the primary indication was refractory bleeding. It is now proposed for the treatment of ascites for the prevention of bleeding and in patients with vascular diseases of the liver. Thus, there are a growing number of patients being treated with TIPS all over the world. The broadening of indications, the involvement of multiple stakeholders, the need for an accurate selection, the positioning in relation to transplantation and the lack of standardization in pre-therapeutic assessment, in the procedure itself and in the follow-up have led the board of the French Association for the Study of the Liver to establish recommendations.

A modified model for predicting mortality after transjugular intrahepatic portosystemic shunt: A multicentre study.

BACKGROUND AND AIMS: The transjugular intrahepatic portosystemic shunt has controversial survival benefits; thus, patient screening should be performed preoperatively. In this study, we aimed to develop a model to predict post-transjugular intrahepatic portosystemic shunt mortality to aid clinical decision making. METHODS: A total of 811 patients undergoing transjugular intrahepatic portosystemic shunt from five hospitals were divided into the training and external validation data sets. A modified prediction model of post-transjugular intrahepatic portosystemic shunt mortality (ModelMT ) was built after performing logistic regression. To verify the improved performance of ModelMT , we compared it with seven previous models, both in discrimination and calibration. Furthermore, patients were stratified into low-, medium-, high- and extremely high-risk subgroups. RESULTS: ModelMT demonstrated a satisfying predictive efficiency in both discrimination and calibration, with an area under the curve of .875 in the training set and .852 in the validation set. Compared to previous models (ALBI, BILI-PLT, MELD-Na, MOTS, FIPS, MELD, CLIF-C AD), ModelMT showed superior performance in discrimination by statistical difference in the Delong test, net reclassification improvement and integrated discrimination improvement (all p < .050). Similar results were observed in calibration. Low-, medium-, high- and extremely high-risk groups were defined by scores of ≤160, 160-180, 180-200 and >200, respectively. To facilitate future clinical application, we also built an applet for ModelMT . CONCLUSIONS: We successfully developed a predictive model with improved performance to assist in decision making for transjugular intrahepatic portosystemic shunt according to survival benefits.

An unusual case of endotipsitis: persistent infection and migration to the right atrium of a transjugular intrahepatic portosystemic shunt (TIPS).

Endotipsitis is an underdiagnosed entity mainly because it requires a high initial level of suspicion. It should be considered in the differential diagnosis of persistent bacteremia in the cirrhotic patient with TIPS. Most cases are treated conservatively with a long-term antibiotherapy, due to the impossibility of surgical removal of the TIPS, except in a liver transplant or autopsy. The patient we present had endotipsitis that manifested as persistent bacteremia with thrombosis of the TIPS. Initially, conservative management with intravenous antibiotherapy was performed; however, due to mechanical complications caused by migration of the original endoprosthesis, it was decided to perform surgery.

The Long-Term Impact of the Tips From Former Smokers® Campaign on Calls to 1-800-QUIT-NOW, 2012-2023.

INTRODUCTION: There is substantial evidence that mass media campaigns increase calls to quitlines and smoking cessation. In 2012, the Centers for Disease Control and Prevention launched the first federally funded national tobacco education campaign, Tips From Former Smokers® (i.e. Tips), which has since aired television advertisements annually. To date, no studies have examined the long-term effect of a national smoking cessation campaign on quitline calls. This study examined the long-term impact of Tips television ads on calls to 1-800-QUIT-NOW from 2012 through 2023. METHODS: Exposure to the Tips campaign was measured using weekly television gross rating points (GRPs) in each U.S. designated market area. We obtained data on calls to 1-800-QUIT-NOW from the National Cancer Institute and used linear regression to model calls to 1-800-QUIT-NOW, from 2012 through 2023, as a function of weekly media market-level GRPs for Tips television ads. Using the regression model results, we calculated predicted values of calls to 1-800-QUIT-NOW across observed GRP values to determine the total additional calls to 1-800-QUIT-NOW that were attributable to the Tips campaign during 2012-2023. RESULTS: Tips GRPs were positively and significantly associated with calls to 1-800-QUIT-NOW across all years (b = 39.94, p < 0.001). Based on this association, we estimate the Tips campaign generated nearly 2.1 million additional calls to 1-800-QUIT-NOW during 2012-2023. CONCLUSIONS: Exposure to the Tips campaign has consistently and significantly increased calls to tobacco quitlines. IMPLICATIONS: Quitlines provide evidence-based support to help people quit smoking. They have been shown to increase the likelihood of successfully quitting. Mass media campaigns have promoted quitline services, and quitline calls have increased significantly with media promotion. The long-term effect of campaigns - like the Centers for Disease Control and Prevention's Tips From Former Smokers® (i.e. Tips) - on quitline calls has not been determined. From 2012 through 2023, exposure to the Tips campaign is estimated to have generated nearly 2.1 million additional calls to 1-800-QUIT-NOW. This study supports continued use of mass media to promote quitlines.

The bacterial displacement test: an in vitro microbiological test for the evaluation of intermittent catheters and urinary tract infection.

AIMS: Intermittent catheters (ICs) are commonly used in bladder management, but catheter-associated urinary tract infections (CAUTIs) remain challenging. Insertion tips may reduce the risk of CAUTIs by minimizing bacterial transfer along the urinary tract. However, there are few laboratory tests to evaluate such technologies. We describe the use of an adapted in vitro urethra agar model to assess bacterial displacement by ICs. METHODS AND RESULTS: Simulated urethra agar channels (UACs) were prepared with catheter-specific sized channels in selective media specific to the challenge organisms. UACs were inoculated with Escherichia coli and Enterococcus faecalis before insertion of ICs, and enumeration of UAC sections was performed following insertion. Four ICs were evaluated: Cure Catheter® Closed System (CCS), VaPro Plus Pocket™, Bard® Touchless® Plus, and SpeediCath® Flex Set. CCS demonstrated significantly reduced bacterial displacement along the UACs compared to the other ICs and was also the only IC with undetectable levels of bacteria toward the end of the UAC (representing the proximal urethra). CONCLUSION: The bacterial displacement test demonstrated significant differences in bacterial transfer between the test ICs with insertion tips, which may reflect their different designs. This method is useful for evaluating CAUTI prevention technology and may help guide future technology innovations.

Predictors and Outcomes of Post-transjugular Intrahepatic Portosystemic Shunt Liver Failure in Patients with Cirrhosis.

BACKGROUND: Post-transjugular intrahepatic portosystemic shunt (TIPS) liver failure (PTLF) is a serious complication of TIPS procedure with poor patient prognosis. This study tried to investigate the incidence of PTLF following elective TIPS procedure and evaluated possible predictive factors for the same. METHODS: A retrospective analysis of patients who underwent elective TIPS placement between 2012 and 2022 and was conducted to determine development of PTLF (≥ 3-fold bilirubin and/or ≥ 2-fold INR elevation from the baseline) within 30 days following TIPS procedure. Medical record review was done and factors predicting development of PTLF and the 90-day transplant-free survival was determined. RESULTS: Thirty of 352 (8.5%) patients developed PTLF within 30 days of TIPS (mean age 54.2 ± 9.8 years, 83% male). The etiology of cirrhosis was related to non-alcoholic steatohepatitis (NASH) in 50%, alcohol in 33.3%, and hepatitis B/C virus infection in 16.7% of the patients. The mean Child-Turcotte-Pugh (CTP) score was 9.5 ± 1.2 and mean model for end stage liver disease (MELD) score was 14.6 ± 4.5 at the time of admission in patients who developed PTLF. The indication for TIPS was recurrent variceal bleed in 50% (15 of 30) and refractory ascites in 46.7% (14 of 30) patients with PTLF. Multivariate analysis identified prior HE (OR 6.1; CI 2.57-14.5, p < 0.0001) and higher baseline CTP score (OR 1.47; CI 1.07-2.04; p = 0.018) as predictors of PTLF. PTLF was associated with significantly lower 90-day transplant-free survival, as compared to patients without PTLF (40% versus 96%, p < 0.001). CONCLUSION: Almost 10% of patients with cirrhosis develop post-TIPS liver failure and is associated with significant early mortality and morbidity. Higher baseline CTP score and prior HE were identified as predictors for PTLF.

A droplet vitrification cryopreservation protocol for conservation of hops (Humulus lupulus) genetic resources.

Hops (Humulus lupulus L.) is essentially used in the brewing industry as it contributes to flavor, and aroma of beer. However, the genetic diversity of hops is increasingly threatened by diseases, environmental changes, and urbanization. Cryopreservation has emerged as a pivotal strategy for safeguarding and maintaining the genetic diversity of hops. The present work presents a comprehensive study on the cryopreservation of hops, focusing on the development and optimization of a droplet vitrification based cryopreservation protocol. Shoot tips excised from one month old in vitro cultures were precultured on 0.3 M sucrose, dehydrated in a loading solution followed by treatment with PVS2 solution for different durations. Significant effect of PVS2 dehydration was observed on post-thaw survival and regeneration after cryoconservation with maximum 50% post-thaw regeneration observed in shoot tips dehydrated in PVS2 for 30 min. Genetic fidelity of the regenerated plants was confirmed using 30 ISSR markers. Reproducibility of the developed protocol was tested on seven other accessions and post thaw regeneration ranging from 43 to 70% was observed across the accessions. The present study reports a highly efficient protocol for conservation of hops germplasm. The results indicate that droplet vitrification can be used as a reliable and sustainable approach for hop genetic preservation, with high survival rates and minimal genetic alterations observed in cryopreserved samples. To the best of our knowledge, this is the first report on DV based cryopreservation of hops germplasm.

Leaks after laparoscopic sleeve gastrectomy: 2024 update on risk factors.

PURPOSE: Leaks after sleeve gastrectomy remain a deadly complication significantly affecting outcomes and medical costs. The aim of the present review is to provide an updated decalogue on leak prevention. METHODS: Risk factors of leakage after LSG were examined based on an extensive review of literature (in period time 2016-2024) and summary of evidence was provided using Oxford levels of evidence scale. RESULTS: Pathogenesis of leakage after LSG still remain related to ischemic and mechanical factors and, therefore, no new evidence has been reported. Conversely, some technical aspect of the procedure has changed: bougie size, antrum resection, staple line reinforcement, and intraoperative leak testing. CONCLUSIONS: Bougie size 36 F is effective and safe achieving similar leakage rate compared to larger bougie sizes (EL:2) 2024 UPDATE; There is no significant difference in the leak rate between restrictive (< 6 cm) and conservative (6 cm) antrum resection (EL: 1) 2024 UPDATE; Surgical experience and case volume affect the leak rate more consistently than every kind of SLR (EL: 2) 2024 UPDATE; Intraoperative leak test after LSG represents a decision based on surgeon preference in absence of standardization (endoscopy, bubble test, methylene blue, indocyanine green.) and strong detection/prevention rate (EL: 3) 2024 UPDATE.

A rare case of severe tricuspid regurgitation caused by TIPS stent migrating into the right atrium.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a common, effective and reliable treatment modality for portal hypertension. Migration of the TIPS stent into the right atrium is a rare and fatal complication. CASE PRESENTATION: We report a case of severe tricuspid regurgitation caused by a stent migrating into the right atrium in a patient hospitalized with refractory ascites due to cirrhosis. DISCUSSION: In this case, it is noteworthy that secondary stenting, which is necessary especially in cases of occlusion, significantly increases the risk of migration. CONCLUSION: Although a rare complication, intracardiac stent migration should be considered in patients with a history of TIPS in the presence of a new heart murmur and signs of arrhythmia.

Neuron navigators: A novel frontier with physiological and pathological implications.

Neuron navigators are microtubule plus-end tracking proteins containing basic and serine rich regions which are encoded by neuron navigator genes (NAVs). Neuron navigator proteins are essential for neurite outgrowth, neuronal migration, and overall neurodevelopment along with some other functions as well. The navigator proteins are substantially expressed in the developing brain and have been reported to be differentially expressed in various tissues at different ages. Over the years, the research has found neuron navigators to be implicated in a spectrum of pathological conditions such as developmental anomalies, neurodegenerative disorders, neuropathic pain, anxiety, cancers, and certain inflammatory conditions. The existing knowledge about neuron navigators remains sparse owing to their differential functions, undiscovered modulators, and unknown molecular mechanisms. Investigating the possible role of neuron navigators in various physiological processes and pathological conditions pose as a novel field that requires extensive research and might provide novel mechanistic insights and understanding of these aspects.

Dynactin 1 negatively regulates HIV-1 infection by sequestering the host cofactor CLIP170.

Many viruses directly engage and require the dynein-dynactin motor-adaptor complex in order to transport along microtubules (MTs) to the nucleus and initiate infection. HIV type 1 (HIV-1) exploits dynein, the dynein adaptor BICD2, and core dynactin subunits but unlike several other viruses, does not require dynactin-1 (DCTN1). The underlying reason for HIV-1's variant dynein engagement strategy and independence from DCTN1 remains unknown. Here, we reveal that DCTN1 actually inhibits early HIV-1 infection by interfering with the ability of viral cores to interact with critical host cofactors. Specifically, DCTN1 competes for binding to HIV-1 particles with cytoplasmic linker protein 170 (CLIP170), one of several MT plus-end tracking proteins (+TIPs) that regulate the stability of viral cores after entry into the cell. Outside of its function as a dynactin subunit, DCTN1 also functions as a +TIP that we find sequesters CLIP170 from incoming particles. Deletion of the Zinc knuckle (Zn) domain in CLIP170 that mediates its interactions with several proteins, including DCTN1, increased CLIP170 binding to virus particles but failed to promote infection, further suggesting that DCTN1 blocks a critical proviral function of CLIP170 mediated by its Zn domain. Our findings suggest that the unique manner in which HIV-1 binds and exploits +TIPs to regulate particle stability leaves them vulnerable to the negative effects of DCTN1 on +TIP availability and function, which may in turn have driven HIV-1 to evolve away from DCTN1 in favor of BICD2-based engagement of dynein during early infection.

Role of Interventional Radiology (IR) in vascular emergencies among cirrhotic patients.

Gastrointestinal hemorrhage remains one of the most common causes of morbidity and mortality among patients with liver cirrhosis. Mostly, these patients bleed from the gastroesophageal varices. However, nonvariceal bleeding is also more likely to occur in these patients. Because of frequent co-existing coagulopathy, cirrhotics are more prone to bleed from a minor vascular injury while performing percutaneous interventions. Ultrasound-guided bedside vascular access is an essential procedure in liver critical care units. Transjugular portosystemic shunts (TIPS) with/without variceal embolization is a life-saving measure in patients with refractory variceal bleeding. Whenever feasible, balloon-assisted retrograde transvenous obliteration (BRTO) is an alternative to TIPS in managing gastric variceal bleeding, but without a risk of hepatic encephalopathy. In cases of failed or unfeasible endotherapy, transarterial embolization using various embolic agents remains the cornerstone therapy in patients with nonvariceal bleeding such as ruptured hepatocellular carcinoma, gastroduodenal ulcer bleeding, and procedure-related hemorrhagic complications. Among various embolic agents, N-butyl cyanoacrylate (NBCA) enables better vascular occlusion in cirrhotics, even in coagulopathy, making it a more suitable embolic agent in an expert hand. This article briefly entails the different interventional radiological procedures in vascular emergencies among patients with liver cirrhosis.

Tips and tricks for a correct interpretation of contrast-enhanced ultrasound.

Although contrast-enhanced ultrasound (CEUS) is a widespread and easily manageable technique, image interpretation errors can occur due to the operator's inexperience and/or lack of knowledge of the frequent pitfalls, which may cause uncertain diagnosis and misdiagnosis. Indeed, knowledge of the basic physical and technical principles of ultrasound is needed both to understand sonographic image findings and to evaluate the potential and limits of the method. Like the B-mode ultrasound, the quality of the CEUS examination is also subject not only to the adequate manual skill of the operator but also to his/her deep knowledge of the technique which improves the quality of the image helping avoid misleading artifacts. In this review, the main parameters influencing a CEUS examination will be described by taking into account the most common errors and pitfalls and their possible solutions.