Regional and temporal variations of spontaneous coronary artery dissection care according to consensus recommendations: a systematic review and meta-analysis.

AIM: The first expert consensus documents on management of patients with spontaneous coronary artery dissection (SCAD) were published in 2018. Worldwide quality of care, as measured by adherence to these recommendations, has not been systematically reviewed. We aim to review the proportion of patients with SCAD receiving consensus recommendations globally, regionally and, determine differences in practice before and after 2018. METHODS AND RESULTS: A systematic review was performed by searching four main databases (Medline, Embase, SCOPUS, CINAHL) from their inception to 16 June 2022. Studies were selected if they included patients with SCAD and reported at least one of the consensus document recommendations. 53 studies, n=8456 patients (mean 50.1 years, 90.6% female) were included. On random effects meta-analysis, 92.1% (95% CI 89.3 to 94.8) received at least one antiplatelet, 78.0% (CI 73.5 to 82.4) received beta-blockers, 58.7% (CI 52.3 to 65.1) received ACE inhibitors or aldosterone receptor blockers (ACEIs/ARBs), 54.4% (CI 45.4 to 63.5) were screened for fibromuscular dysplasia (FMD), and 70.2% (CI 60.8 to 79.5) were referred to cardiac rehabilitation. Except for cardiac rehabilitation referral and use of ACEIs/ARBs, there was significant heterogeneity in all other quality-of-care parameters, across geographical regions. No significant difference was observed in adherence to recommendations in studies published before and after 2018, except for lower cardiac rehabilitation referrals after 2018 (test of heterogeneity, p=0.012). CONCLUSION: There are significant variations globally in the management of patients with SCAD, particularly in FMD screening. Raising awareness about consensus recommendations and further prospective evidence about their effect on outcomes may help improve the quality of care for these patients.

Plastic waste in sandy beaches and surface water in Thanh Hoa, Vietnam: abundance, characterization, and sources.

The occurrence and characterization of marine debris on beaches bring opportunities to track back the anthropogenic activities around shorelines as well as aid in waste management and control. In this study, the three largest beaches in Thanh Hoa (Vietnam) were examined for plastic waste, including macroplastics (≥ 5 mm) on sandy beaches and microplastics (MPs) (< 5 mm) in surface water. Among 3803 items collected on the beaches, plastic waste accounted for more than 98%. The majority of the plastic wastes found on these beaches were derived from fishing boats and food preservation foam packaging. The FT-IR data indicated that the macroplastics comprised 77% polystyrene, 17% polypropylene, and 6% high-density polyethylene, while MPs discovered in surface water included other forms of plastics such as polyethylene- acrylate, styrene/butadiene rubber gasket, ethylene/propylene copolymer, and zein purified. FT-IR data demonstrated that MPs might also be originated from automobile tire wear, the air, and skincare products, besides being degraded from macroplastics. The highest abundance of MPs was 44.1 items/m3 at Hai Tien beach, while the lowest was 15.5 items/m3 at Sam Son beach. The results showed that fragment form was the most frequent MP shape, accounting for 61.4 ± 14.3% of total MPs. MPs with a diameter smaller than 500 µm accounted for 70.2 ± 7.6% of all MPs. According to our research, MPs were transformed, transported, and accumulated due to anthropogenic activities and environmental processes. This study provided a comprehensive knowledge of plastic waste, essential in devising long-term development strategies in these locations.

Factors Affecting Hospital Length of Stay in Geriatric Patients With a Surgically Treated Fragility Ankle Fracture.

Fragility ankle fractures in elderly have a rising incidence and hospitalization may be prolonged due to pre-existing comorbidities, compromised soft tissue and postoperative difficulties in the rehabilitation process. The aim of this retrospective cohort study was to investigate risk factors for longer total hospitalization duration in elderly patients with surgically treated fragility (Lauge Hansen supination external rotation type 4) fractures. We included all patients ≥ 70 years with a fragility fracture, who were treated surgically between 2011 and 2019 (n = 97) in a level 1 and 2 trauma center. Data on patient demographics, fracture characteristics, surgical treatment strategies and postoperative complications were retrieved from medical records. Multivariate regression analysis was performed to identify independent risk factors for longer hospitalization duration. The mean age of the included patients was 78.27 (± 6.56) years; 71 patients (73.20%) were female. Ten fractures (10.30%) were classified as open and 49 (50.50%) as a luxation type fracture. Fifty-nine patients (60.80%) were hospitalized after admission to the emergency department. External fixation was performed in 34 patients (35.10%) and served as bridge to definitive fixation in 29 patients (85.30%). The mean total hospital length of stay of all patients was 7.04 (± 6.58) days. Multivariate regression analysis demonstrated that the use of external fixation (p < .001) and the postoperative discharge destination (p < .001) were independently associated with a prolonged hospital stay. External fixation and discharge destination were independent risk factors for a prolonged hospital stay in elderly patients with a fragility fracture.

Combined Therapy With Avastin, a PAF Receptor Antagonist and a Lipid Mediator Inhibited Glioblastoma Tumor Growth.

Glioblastoma multiforme (GBM) is an aggressive, highly proliferative, invasive brain tumor with a poor prognosis and low survival rate. The current standard of care for GBM is chemotherapy combined with radiation following surgical intervention, altogether with limited efficacy, since survival averages 18 months. Improvement in treatment outcomes for patients with GBM requires a multifaceted approach due to the dysregulation of numerous signaling pathways. Recently emerging therapies to precisely modulate tumor angiogenesis, inflammation, and oxidative stress are gaining attention as potential options to combat GBM. Using a mouse model of GBM, this study aims to investigate Avastin (suppressor of vascular endothelial growth factor and anti-angiogenetic treatment), LAU-0901 (a platelet-activating factor receptor antagonist that blocks pro-inflammatory signaling), Elovanoid; ELV, a novel pro-homeostatic lipid mediator that protects neural cell integrity and their combination as an alternative treatment for GBM. Female athymic nude mice were anesthetized with ketamine/xylazine, and luciferase-modified U87MG tumor cells were stereotactically injected into the right striatum. On post-implantation day 13, mice received one of the following: LAU-0901, ELV, Avastin, and all three compounds in combination. Bioluminescent imaging (BLI) was performed on days 13, 20, and 30 post-implantation. Mice were perfused for ex vivo MRI on day 30. Bioluminescent intracranial tumor growth percentage was reduced by treatments with LAU-0901 (43%), Avastin (77%), or ELV (86%), individually, by day 30 compared to saline treatment. In combination, LAU-0901/Avastin, ELV/LAU-0901, or ELV/Avastin had a synergistic effect in decreasing tumor growth by 72, 92, and 96%, respectively. Additionally, tumor reduction was confirmed by MRI on day 30, which shows a decrease in tumor volume by treatments with LAU-0901 (37%), Avastin (67%), or ELV (81.5%), individually, by day 30 compared to saline treatment. In combination, LAU-0901/Avastin, ELV/LAU-0901, or ELV/Avastin had a synergistic effect in decreasing tumor growth by 69, 78.7, and 88.6%, respectively. We concluded that LAU-0901 and ELV combined with Avastin exert a better inhibitive effect in GBM progression than monotherapy. To our knowledge, this is the first study that demonstrates the efficacy of these novel therapeutic regimens in a model of GBM and may provide the basis for future therapeutics in GBM patients.

Human Chondrocytes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Seeded on a Dermal-Derived Collagen Matrix Sheet: Our Preliminary Results for a Ready to Go Biotechnological Cartilage Graft in Clinical Practice.

BACKGROUND: The articular cartilage is unique in that it contains only a single type of cell and shows poor ability for spontaneous healing. Cartilage tissue engineering which uses mesenchymal stem cells (MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs) is considered an attractive treatment for cartilage lesions and osteoarthritis. The establishment of cartilage regenerative medicine is an important clinical issue, but the search for cell sources able to restore cartilage integrity proves to be challenging. The aim of this study was to create cartilage grafts from the combination of AT-MSCs and collagen substrates. METHODS: Mesenchymal stem cells were obtained from human donors' adipose tissue, and collagen scaffold, obtained from human skin and cleaned from blood vessels, adipose tissues, and debris, which only preserve dermis and epidermis, were seeded and cultured on collagen substrates and differentiated to chondrocytes. The obtained chondrocyte extracellular matrix of cartilage was then evaluated for the expression of chondrocyte-/cartilage-specific markers, the Cartilage Oligomeric Matrix Protein (COMP), collagen X, alpha-1 polypeptide (COL10A1), and the Collagen II, Human Tagged ORF Clone (COL2A1) by using the reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Our findings have shown that the dermal collagen may exert important effects on the quality of in vitro expanded chondrocytes, leading in this way that the influence of collagen skin matrix helps to produce highly active and functional chondrocytes for long-term cartilage tissue regeneration. CONCLUSION: This research opens up the possibility of generating cartilage grafts with the precise purpose of improving the existing limitation in current clinical procedures.

Requirement of GTP binding for TIF-90-regulated ribosomal RNA synthesis and oncogenic activities in human colon cancer cells.

Transcription initiation factor 90 (TIF-90), an alternatively spliced variant of TIF-IA, differs by a 90 base pair deletion of exon 6. TIF-90 has been shown to regulate ribosomal RNA (rRNA) synthesis by interacting with polymerase I (Pol I) during the initiation of ribosomal DNA (rDNA) transcription in the nucleolus. Recently, we showed that TIF-90-mediated rRNA synthesis can play an important role in driving tumorigenesis in human colon cancer cells. Here we show that TIF-90 binds GTP at threonine 310, and that GTP binding is required for TIF-90-enhanced rRNA synthesis. Overexpression of activated AKT induces TIF-90 T310, but not a GTP-binding site (TIF-90 T310N) mutant, to translocate into the nucleolus and increase rRNA synthesis. Complementing this result, treatment with mycophenolic acid (MPA), an inhibitor of GTP production, dissociates TIF-90 from Pol I and hence abolishes AKT-increased rRNA synthesis by way of TIF-90 activation. Thus, TIF-90 requires bound GTP to fulfill its function as an enhancer of rRNA synthesis. Both TIF variants are highly expressed in colon cancer cells, and depletion of TIF-IA expression in these cells results in significant sensitivity to MPA-inhibited rRNA synthesis and reduced cell proliferation. Finally, a combination of MPA and AZD8055 (an inhibitor of both AKT and mTOR) synergistically inhibits rRNA synthesis, in vivo tumor growth, and other oncogenic activities of primary human colon cancer cells, suggesting a potential avenue for the development of therapeutic treatments by targeting the regulation of rRNA synthesis by TIF proteins.

Nationwide study of the treatment of mycotic abdominal aortic aneurysms comparing open and endovascular repair in The Netherlands.

OBJECTIVE: Mycotic aneurysms of the abdominal aorta (MAAA) can be treated by open repair (OR) or endovascular aneurysm repair (EVAR). This nationwide study provides an overview of the situation of MAAA treatment in The Netherlands in 2016. METHODS: A retrospective cohort study was conducted with all centers that registered aortic abdominal aneurysms in the Dutch Surgical Aneurysm Audit in 2016. Questionnaires on 1-year outcomes were sent to all centers that treated patients with MAAA. The primary aim was to determine 30-day and 1-year mortality and morbidity of OR- and EVAR-treated patients. Morbidity was determined by the need for reoperations and the number of readmissions to the hospital. RESULTS: Twenty-six MAAA were detected in the Dutch Surgical Aneurysm Audit database of 2016, resulting in an incidence of 0.7% of all registered abdominal aortic aneurysms. The 30-day mortality for OR and EVAR treated patients was 1 in 13 and 0 in 13, respectively. Major and minor reinterventions within 30 days were needed for two (one OR and one EVAR) and two (one OR and one EVAR) patients, respectively. Two patients (15.4%) in the OR group and one patient (7.7%) in the EVAR group were readmitted to hospital within 30 days. In total, 1-year outcomes of 23 patients were available. In the OR group, one patient (9.1%) died in the first postoperative year. There was one major reintervention (removal of endoprosthesis and spiralvein reconstruction) in the EVAR group. Two patients (18.2%) treated with OR and two (16.7%) treated with EVAR required a minor reintervention. In both groups, four patients (OR, 36.4%; EVAR, 33.3%) were readmitted to hospital within 1 year postoperatively. CONCLUSIONS: Both OR- and EVAR-treated patients show acceptable clinical outcomes after 30 days and at the 1-year follow-up. Depending on the clinical course of the patient, EVAR may be considered in the management of this disease.

Ebp1 p48 promotes oncogenic activities in human colon cancer cells through regulation of TIF-90-mediated ribosomal RNA synthesis.

The ErbB3-binding protein 1 (Ebp1) has been reported as either an oncogenic regulator or a tumor suppressor in a variety of cancers. Here, we show that Ebp1 p48, a predominant expression isoform, is highly expressed in the majority of human colon tumor cells compared with normal adjacent tissues and its expression is required for the oncogenic activities of these cells. Depletion of Ebp1 expression in primary colon cancer cells inhibits cell proliferation, colony forming, and invasion in vitro as well as tumor formation in vivo and enhances cell sensitivity to irradiation. We further demonstrated that Ebp1 interacts with TIF-90, a splice variant of transcription initiation factor IA (TIF-IA) of the RNA polymerase I complex, allowing for regulation of ribosomal RNA (rRNA) synthesis and oncogenesis in human colon cancer cells. Moreover, Ebp1 expression is essential for Akt protected TIF-90 stability by preventing TIF-90's ubiquitination by Mdm2 and hence, its proteasomal degradation. The results of the present study support a mechanism of underlying oncogenic activities by means of Ebp1 through regulation of TIF-90-mediated rRNA synthesis and suggest the potential therapeutic treatment of colon cancer by targeting Ebp1 and its signaling.

The Bcl-2 inhibitor venetoclax inhibits Nrf2 antioxidant pathway activation induced by hypomethylating agents in AML.

Induction of reactive oxygen species (ROS), an important process for the cytotoxicity of various acute myeloid leukemia (AML) therapies including hypomethylating agents (HMAs), concurrently activates the NF-E2-related factor 2 (Nrf2) antioxidant response pathway which in turn results in induction of antioxidant enzymes that neutralize ROS. In this study, we demonstrated that Nrf2 inhibition is an additional mechanism responsible for the marked antileukemic activity in AML seen with the combination of HMAs and venetoclax (ABT-199). HMA and venetoclax combined treatment augmented mitochondrial ROS induction and apoptosis compared with treatment HMA alone. Treatment of AML cell lines as well as primary AML cells with venetoclax disrupted HMA decitabine-increased nuclear translocation of Nrf2 and induction of downstream antioxidant enzymes including heme oxygenase-1 and NADP-quinone oxidoreductase-1. Venetoclax treatment also leads to dissociation of B-cell lymphoma 2 from the Nrf2/Keap-1 complex and targets Nrf2 to ubiquitination and proteasomal degradation. Thus, our results here demonstrated an undiscovered mechanism underlying synergistic effect of decitabine and venetoclax in AML cells, elucidating for impressive results in antileukemic activity against AML in preclinical and early clinical studies by combined treatment of these drugs.

The role of ErbB3 binding protein 1 in cancer: Friend or foe?

ErbB3, a member of the epidermal growth factor receptor family, reportedly plays an essential role in the regulation of cancer progression and therapeutic resistance. Numerous studies have indicated that ErbB3 binding protein 1 (Ebp1), a binding partner for ErbB3, plays an important regulatory role in the expression and function of ErbB3, but there is no agreement as to whether Ebp1 also has an ErbB3-independent function in cancer and how it might contribute to tumorigenesis. In this review, we will discuss the different functions of the two Ebp1 isoforms, p48 and p42, that may be responsible for the potentially dual role of Ebp1 in cancer growth.