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The SET-domain containing protein 2 (SETD2) is a protein lysine methyltransferase that has been shown to methylate the super-substrate peptide ssK36 100 times faster than the corresponding natural H3K36 peptide. Here, a combination of molecular dynamics simulations and biochemical experiments are applied to identify the mechanisms responsible for the increased activity of SETD2 towards ssK36.

Purpose: To evaluate access site adverse events following ClotTriever-mediated large-bore mechanical thrombectomy via small upper extremity deep veins (< 6-mm). Materials and methods: Twenty patients, including 24 upper extremity venous access sites, underwent ClotTriever-mediated large-bore thrombectomy of the upper extremity and thoracic central veins for symptomatic deep vein obstruction unresponsive to anticoagulation. Patients without follow-up venous duplex examinations (n = 3) were excluded. Patients who had > 6-mm diameter veins accessed (n = 3) were excluded. Temporary purse-string sutures and manual pressure were used for access site hemostasis in all patients. Vein access site and diameter, technical success (defined as placement of the 13.5-French ClotTriever sheath followed by thrombectomy), and early (< 30-days) and late (> 30-days) access site-related adverse events (according to the Adverse Event Classification by the Society of Interventional Radiology criteria) were recorded. Results: Fourteen patients (8 males, 6 females; mean age 51.7 ± 13.6 years) comprising 16 upper extremity venous access sites were included in this study. Access sites included: right brachial (n = 7), left brachial (n = 5), and bilateral brachial (n = 2) veins. The mean access site diameter was 4.3-mm ± 0.67-mm. Technical success was achieved via all access sites. Six (42.9%) patients underwent stent reconstruction following thrombectomy through the same accesses. After the procedure, all purse-string sutures were removed within 24 h. Three (21.4%) patients experienced small access site hematomas that did not require transfusion, intervention, or prolonged hospitalization. Initial follow-up venous duplex ultrasounds were performed at 29.3 ± 21.7 days following intervention. The mean follow-up interval to the second and third venous duplex ultrasounds were 124.3 ± 64-days and 225.1 ± 80.1 days, respectively. One (7.1%) patient developed right arm swelling six days after the procedure and was found to have thrombosis of the previously accessed right brachial vein. No other clinically or sonographically significant access site adverse events were observed. Conclusion: ClotTriever-mediated large-bore thrombectomy via small upper extremity veins is safe with minimal access site adverse events. [ABSTRACT FROM AUTHOR]

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Simple Summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and early detection plays a crucial role in improving patient survival. However, the current surveillance guidelines may not fully address the growing number of HCC cases in individuals with non-alcoholic fatty liver disease (NAFLD), who often develop cancer without liver cirrhosis. Our paper aims to review and compare major international guidelines on HCC surveillance, highlighting key gaps in their criteria such as the exclusion of non-cirrhotic NAFLD patients. By exploring advancements in screening technologies, including imaging and biomarkers, we aim to provide insights that could lead to better detection methods for high-risk populations. These findings have the potential to shape future research and updates to clinical guidelines, ensuring that surveillance strategies become more inclusive and effective. Background/Objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, with prognosis and treatment outcomes that are significantly influenced by the stage at diagnosis. Early detection through regular surveillance is crucial for improving patient outcomes, especially in high-risk groups such as those with cirrhosis or chronic hepatitis B. Geographic variations in HCC risk factors, including viral hepatitis and non-alcoholic fatty liver disease (NAFLD), have led to the development of different international surveillance guidelines. This review aims to compare and evaluate the surveillance strategies proposed by the Asian Pacific Association for the Study of the Liver (APASL), the American Association for the Study of Liver Diseases (AASLD), and the European Association for the Study of the Liver and European Organization for Research and Treatment of Cancer (EASL–EORTC). Methods: The review examined and compared major international guidelines on HCC surveillance, focusing on patient selection, imaging modalities, and the integration of biomarkers. We also explored recent advancements in screening techniques, including artificial intelligence and emerging biomarkers, to identify future directions for improving surveillance strategies. Results: Our analysis identified key differences in the guidelines, particularly in imaging modality preferences and the use of biomarkers for early detection. While all guidelines place emphasis on high-risk populations, the inclusion criteria and surveillance intervals vary. Additionally, novel technologies such as artificial intelligence show potential to enhance the accuracy and efficiency of HCC detection. Conclusions: This review highlights the need to harmonize the international guidelines, particularly in regard to patients with non-cirrhotic NAFLD who remain under-represented in current surveillance protocols. Future research should focus on integrating emerging technologies and biomarkers to improve early detection and overall patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: In the present report, we have described the technical and clinical outcomes of percutaneous thrombectomy in the deep veins of the upper extremity and thorax using the ClotTriever system (Inari Medical, Irvine, CA). Methods: Fourteen patients with symptomatic deep venous occlusive disease in the upper extremity deep veins and thoracic central veins who had undergone thrombectomy using the ClotTriever system between October 2020 and January 2022 were reviewed. The technical results, adverse events, imaging follow-up data, and clinical outcomes were recorded. Results: Fourteen patients (seven men and seven women; mean age, 53.6 ± 13.3 years) constituted the study cohort. Of the 14 patients, 9 (64.3%) had had DVT due to intravascular invasion or external compression from known malignancy, 2 (14.3%) had had infected thrombi and/or vegetation due to Staphylococcus aureus refractory to intravenous antibiotic therapy, and 3 (21.4%) had had a benign etiology for thrombus formation. The presenting symptoms included upper extremity and/or facial swelling (n = 14), upper extremity pain (n = 6), fever (n = 2), and dyspnea (n = 1). Thrombectomy with the ClotTriever system was successfully completed in all 14 patients. Seven patients (50.0%) had required additional venous stent reconstruction after thrombectomy to address the underlying stenosis. No major adverse events were noted. All the patients had experienced resolution of the presenting symptoms. Conclusions: For the management of symptomatic deep venous occlusive disease of the upper extremity deep veins and thoracic central veins, thrombectomy using the ClotTriever system was feasible with excellent technical and clinical success.

Abstract Objectives Two pilot studies of AR‐42, a pan‐histone deacetylase inhibitor, in human neurofibromatosis type 2 (NF2), vestibular schwannomas (VS), and meningiomas are presented. Primary endpoints included safety, and intra‐tumoral pharmacokinetics (PK) and pharmacodynamics (PD). Methods Pilot 1 is a subset analysis of a phase 1 study of AR‐42 in solid tumors, which included NF2 or sporadic meningiomas. Tumor volumes and treatment‐related adverse events (TRAEs) are reported (NCT01129193). Pilot 2 is a phase 0 surgical study of AR‐42 assessing intra‐tumoral PK and PD. AR‐42 was administered for 3 weeks pre‐operatively. Plasma and tumor drug concentrations and p‐AKT expression were measured (NCT02282917). Results Pilot 1: Five patients with NF2 and two with sporadic meningiomas experienced a similar incidence of TRAEs to the overall phase I trial. The six evaluable patients had 15 tumors (8 VS, 7 meningiomas). On AR‐42, tumor volume increased in six, remained stable in eight, and decreased in one tumor. The annual percent growth rate decreased in eight, remained stable in three, and increased in four tumors. Pilot 2: Four patients with sporadic VS and one patient with meningioma experienced no grade 3/4 toxicities. Expression of p‐AKT decreased in three of four VS. All tumors had higher AR‐42 concentrations than plasma. Conclusions AR‐42 is safe. Tumor volumes showed a mixed response, but most slowed growth. On a 40‐mg regimen, drug concentrated in tumors and growth pathways were suppressed in most tumors, suggesting this may be a well‐tolerated and effective dose. A phase 2 study of AR‐42 for NF2‐associated tumors appears warranted. Level of Evidence 1b, 4.

Twitter use by physicians, including those in the hematology-oncology field, is increasing. This microblogging platform provides a means to communicate and collaborate on a global scale. For the oncology professional, an active Twitter presence provides opportunities for continuing medical education, patient engagement and education, personal branding, and reputation management. However, because Twitter is an open, public forum, potential risks such as patient privacy violations, personal information disclosures, professionalism lapses, and time management need to be considered and managed. The authors have summarized the benefits and risks of Twitter use by the hematology-oncology physician. In addition, strategies to maximize benefit and minimize risk are discussed, and resources for additional learning are provided.

Primary liver cancer is the leading cause of cancer-related deaths worldwide. with incidences predicted to rise over the next several decades. Locoregional therapies, such as radiofrequency or microwave ablation, are described as image-guided percutaneous procedures, which offer either a curative intent for early-stage hepatocellular carcinoma or bridging/downstaging for surgical resection or transplantation. Catheter-driven locoregional therapies, such as transarterial chemoembolization and radioembolization, induce tumor hypoxia, can be palliative, and improve survival for early-to-intermediate hepatocellular carcinoma and unresectable intrahepatic cholangiocarcinoma. Herein, we provide a comprehensive overview of the antineoplastic mechanisms underpinning locoregional therapies, different treatment approaches, and the current state of the literature for the efficacy of locoregional therapies for primary liver cancer. We also discuss emerging advancements, such as the adjuvant use of immunotherapies and molecular targeting agents with locoregional therapy, for the treatment of primary liver cancer.

Advancements in artificial intelligence (AI) have significantly transformed the field of abdominal radiology, leading to an improvement in diagnostic and disease management capabilities. This narrative review seeks to evaluate the current standing of AI in abdominal imaging, with a focus on recent literature contributions. This work explores the diagnosis and characterization of hepatobiliary, pancreatic, gastric, colonic, and other pathologies. In addition, the role of AI has been observed to help differentiate renal, adrenal, and splenic disorders. Furthermore, workflow optimization strategies and quantitative imaging techniques used for the measurement and characterization of tissue properties, including radiomics and deep learning, are highlighted. An assessment of how these advancements enable more precise diagnosis, tumor description, and body composition evaluation is presented, which ultimately advances the clinical effectiveness and productivity of radiology. Despite the advancements of AI in abdominal imaging, technical, ethical, and legal challenges persist, and these challenges, as well as opportunities for future development, are highlighted. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common primary renal malignancy. Prevalence of RCC in developed countries has slowly increased. Although partial or total nephrectomy has been the first-line treatment for early-stage RCC, improved or similar safety and treatment outcomes with locoregional therapies have challenged this paradigm. In this review, we explore locoregional techniques for early-stage RCC, including radiofrequency ablation, cryoablation, and microwave ablation with a focus on procedural technique, patient selection, and safety/treatment outcomes. Furthermore, we discuss future advances and novel techniques, including radiomics, combination therapy, high-intensity focused ultrasound, and catheter-directed techniques. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate outcomes including safety and efficacy of drug-eluting bead trans-arterial chemo-embolization (DEB-TACE) in the treatment of locally advanced hepatocellular carcinoma (LA-HCC). Materials and methods: In this single-center, retrospective study, we evaluated 471 consecutive patients with LA-HCC who underwent DEB-TACE from 2015 to 2020. Efficacy of DEB-TACE was assessed based on the imaging response using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the biochemical response using alpha-fetoprotein (AFP) levels at 1-month follow-up. Adverse events, progression free survival (PFS), and overall survival were also examined. Results: HCC distribution was bilobar in 49% with largest lesion mean size of 4.3 cm ± 3.2, and a majority of patients (46.7%) were Barcelona Club Liver Cancer (BCLC) stage B. Complete radiologic response was achieved in 120 (25.5%) patients, comparable to a reported 28% rate for conventional TACE. Biochemically, 41 (8.7%) patients achieved complete response, and 113 (24%) had a partial response. A total of 59 (12.5%) patients were successfully bridged to liver transplantation. Major adverse events were observed in 3%, while 7.2% experienced post-embolization syndrome. Mean PFS was 6.7 months ± 6.6, and overall survival was 64%, 16.3%, 2.1% at 1, 3, and 5 years, respectively. Conclusion: Based on our real world experience at a single center, DEB-TACE remains the locoregional therapy of choice for LA-HCC due to its favorable safety and efficacy profile. [ABSTRACT FROM AUTHOR]

Introduction: Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy. Methods: Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times—today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome‐related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics. Results: A total of 219 patients (median [range] age 71 [65–88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible". Conclusion: Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient‐defined priorities and include them in decision‐making. In this secondary analysis of 219 older participants (median age 71 years) from a randomized trial addressing vulnerabilities in older adults with cancer, 61% prioritized survival over other outcomes such as maintaining their independence or being free from symptoms. Clinicians should elicit patient‐defined priorities and include them in decision‐making when discussing treatment. [ABSTRACT FROM AUTHOR]