Protective effect of trans-nerolidol on vascular endothelial cell injury induced by lipopolysaccharides / Efectos protectores del trans-nerolidol en lesiones inducidas por lipopolisacáridos en células endoteliales vasculares

This article aimed to discuss the protection of trans - nerolidol on vascular endothelial cells (ECs) injured by lipopolysac charides. ECs were divided into four groups: normal, model, low and high dose trans - nerolidol treatment groups. The cell survival rate and the contents of NO in the cell culture supernatant were determined. The protein expression and transcript level of pe roxisome proliferator - activated receptor - γ (PPARγ), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by western blotting and RT - PCR respectively. Compared with the normal group, cell livability, protein e xpression and mRNA transcript level of PPARγ and eNOS decreased, NO contents, protein expression and mRNA transcript tlevel of iNOS increased in model group significantly. Compared with model group, all the changes recovered in different degree in treatmen t groups. Hence, it was concluded that trans - nerolidol can alleviate the ECs injuryby the regulation of iNOS/eNOS through activating PPARγ in a dose - dependent manner

Este artículo tiene como objetivo discutir la protección del trans - nerolidol en las células endoteliales vasculares (CE) dañadas por lipopolisacáridos. Las CE se di vidieron en cuatro grupos: normal, modelo, grupos de tratamiento con trans - nerolidol de baja y alta dosis. Se determinó la tasa de supervivencia de las células y los contenidos de óxido nítrico (NO) en el sobrenadante del cultivo celular. La expresión de p roteínas y el nivel de transcripción del receptor activado por proliferadores de peroxisomas - γ (PPARγ), el óxido nítrico sint et asa endotelial (eNOS) y el óxido nítrico sint et asa inducible (iNOS) se determinaron mediante western blot y RT - PCR, respectivamen te. En comparación con el grupo normal, la viabilidad celular, la expresión de proteínas y el nivel de transcripción de PPARγ y eNOS disminuyeron, los contenidos de NO, la expresión de proteínas y el nivel de transcripción de iNOS aumentaron significativam ente en el grupo modelo. En comparación con el grupo modelo, todos los cambios se recuperaron en diferentes grados en los grupos de tratamiento. Por lo tanto, se concluyó que el trans - nerolidol puede aliviar el daño en las CE regulando iNOS/eNOS a través d e la activación de PPARγ de manera dependiente de la dosis.

Competências do enfermeiro no cuidado a pacientes com acidente vascular cerebral elegíveis à terapia trombolítica / Competencias de enfermería en el cuidado de personas con accidente cerebrovascular elegibles para terapia trombolítica / Nursing competencies in the care of patients with stroke who are eligible for thrombolytic therapy

Resumo Introdução: O acidente vascular cerebral isquêmico tem como tratamento a terapia trombolítica, aplicada ainda na fase aguda, promovendo melhora importante nas sequelas acarretadas por este agravo. Considerando a complexidade da terapia trombolítica, torna-se necessário que os enfermeiros compreendam suas competências para auxiliar no cuidado. Objetivo: Identificar evidências científicas acerca das competências do enfermeiro no cuidado a pacientes com acidente vascular cerebral elegíveis à terapia trombolítica. Metodologia: Revisão integrativa composta por seis etapas em seis etapas (elaboração da questão, busca na literatura, coleta de dados, análise, discussão e apresentação da revisão), realizada nas bases de dados MEDLINE, LILACS, BDENF, IBECS, PubMed, Scopus, Web of Science, Embase e CINAHL. A busca foi realizada entre agosto e setembro de 2022 adotando como critérios de inclusão estudos primários; gratuitos, disponíveis eletronicamente na íntegra; nos idiomas inglês, português e espanhol. Foram obtidos inicialmente 2.830 estudos, os quais passaram por uma seleção, onde foram incluídos aqueles que atendiam os critérios previamente estabelecidos. Resultados: Com base nos doze estudos incluídos nesta revisão identificaram-se competências voltadas à três atividades do cuidado: gestão do cuidado como trabalho em equipe, códigos, fluxos e protocolos, assistência ao paciente antes, durante e após a utilização da terapia trombolítica e educação em saúde para equipe, pacientes e familiares. Conclusão: Os achados desta revisão puderam evidenciar as competências do enfermeiro no cuidado aos pacientes elegíveis a terapia trombolítica, as quais perpassam diferentes áreas de atuação do enfermeiro. Para este estudo prevaleceram as competências assistências, seguida por competências gerenciais.

Resumen Introducción: El accidente cerebrovascular isquémico se trata con terapia trombolítica, aplicada incluso en la fase aguda, que promueve una mejoría significativa de las secuelas provocadas por este padecimiento. Considerando la complejidad de la terapia trombolítica, es necesario que las personas profesionales de enfermería comprendan sus competencias para ayudar en el cuidado. Objetivo: Identificar evidencias científicas sobre las competencias del personal de enfermería en el cuidado de pacientes con accidente cerebrovascular elegibles para terapia trombolítica. Metodología: Revisión integradora que consta de seis etapas (elaboración de la pregunta, búsqueda bibliográfica, recolección de datos, análisis, discusión y presentación de la revisión), realizada en las bases de dados MEDLINE, LILACS, BDENF, IBECS, PubMed, Scopus, Web of Science, Embase y CINAHL. La búsqueda se realizó entre agosto y septiembre de 2022. Los criterio de inclusión fueron: estudios primarios, gratuito, disponible electrónicamente en su totalidad, en inglés, portugués y español. Inicialmente se obtuvieron 2830 estudios, los cuales fueron sometidos a un proceso de selección, que incluyó aquellos que cumplían con los criterios previamente establecidos. Resultados: A partir de los doce estudios incluidos en esta revisión, se identificaron competencias centradas en tres actividades asistenciales: gestión del cuidado como trabajo en equipo, códigos, flujos y protocolos, atención a pacientes antes, durante y después del uso de la terapia trombolítica y educación en salud para personal, pacientes y familias. Conclusión: Los hallazgos de esta revisión pudieron resaltar las competencias de las personas profesionales en enfermería en el cuidado de personas elegibles para terapia trombolítica, que abarcan diferentes áreas de actuación del personal de enfermería. Para este estudio, prevalecieron las habilidades asistenciales, seguidas de las competencias gerenciales.

ABSTRACT Introduction: Ischemic stroke is treated with thrombolytic therapy, applied even in the acute phase, promoting a significant improvement in the after-effects caused by this condition. Considering the complexity of thrombolytic therapy, it is necessary for nurses to understand the skills required to assist in care. Objective: To identify scientific evidence about the competencies of nurses in the care of patients with stroke who are eligible for thrombolytic therapy. Methodology: An integrative review consisting of six stages (elaboration of the question, literature review, data collection, analysis, discussion, and presentation), conducted in MEDLINE, LILACS, BDENF, IBECS, PubMed, Scopus, Web of Science, Embase, and CINAHL databases. The search was carried out between August and September 2022 using primary studies as the inclusion criteria: free of charge, fully available electronically, published in English, Portuguese, or Spanish. Initially, 2.830 studies were obtained, which underwent a selection process that included only those studies that met the previously established criteria. Results: Based on the twelve studies included in this review, competencies focused on three care activities were identified: care management such as teamwork; codes; flows and protocols; patient care before, during, and after the use of thrombolytic therapy; and education health education for staff, patients, and families. Conclusion: The findings of this review highlighted the nurses' competencies in the care of patients eligible for thrombolytic therapy, which encompass different areas of the nurse's work. For this study, assistance competencies prevailed, followed by management competencies.

Transcarotid vascular access for transcatheter aortic valve implantation: is choosing the left side always right?

BACKGROUND: The transcarotid (TC) vascular access for transcatheter aortic valve implantation (TAVI) has emerged as the first-choice alternative to the transfemoral access, in patients unsuitable for the latter. The use of both the left and right common carotid arteries (CCAs) for TC-TAVI has been described, but the optimal side is subject to debate. We conducted this pilot study to compare the level of vessel tortuosity and plaque burden from either the left CCA to the aortic annulus, or the right CCA to the aortic annulus, considering them as surrogates for technical and procedural complexity. METHODS: Consecutive patients who underwent TC-TAVI between 2018 and 2021 in our institution were included. Using three-dimensional reconstruction, pre-TAVI neck and chest computed tomography angiography exams were reviewed to assess the tortuosity index (TI), sum of angles metric, as well as plaque burden, between each CCA and the aortic annulus. RESULTS: We included 46 patients who underwent TC-TAVI. No significant difference regarding the mean TIs between the left and right sides (respectively 1.20 and 1.19, p = 0.82), the mean sum of angles (left side: 396°, right side: 384°, p = 0.27), and arterial plaque burden (arterial plaque found in 30% of left CCAs and 45% of right CCAs, p = 0.19) was found. CONCLUSIONS: We found no convincing data favoring the use of one particular access side over the other one. The choice of the CCA side in TC-TAVI should to be made on a case-by-case basis, in a multidisciplinary fashion, and may also depend on the operators' experience.

Paradigm Shifts in Vascular Surgery: Analysis of the Top 100 Innovative and Disruptive Academic Publications.

BACKGROUND: Disruption score (DS) is a novel bibliometric created to identify research that shifts paradigms, which may be overlooked by citation count (CC). We analyzed the most disruptive, compared to the most cited, literature in vascular surgery, and hypothesized that DS and CC would not correlate. METHODS: A PubMed search identified vascular surgery publications from 1954 to 2014. The publications were linked to the iCite NIH tool and DS algorithm to identify the top 100 studies by CC and DS, respectively. The publications were reviewed for study focus, design, and contribution, and subsequently compared. RESULTS: A total of 56,640 publications were identified. The top 100 DS papers were frequently published in J Vasc Sur (43%) and Eur J Vasc Endovasc Surg (13%). The top 100 CC papers were frequently published in N Engl J Med (32%) and J Vasc Sur (20%). The most cited article is the fifth most disruptive; the most disruptive article is not in the top 100 cited papers. The DS papers had a higher mean DS than the CC papers (.17 vs .0001, P < .0001). The CC papers had a higher mean CC than the DS papers (866 vs 188, P < .0001). DS and CC are weakly correlated metrics (r = .22, P = .03). DISCUSSION: DS was weakly correlated with CC and captured a unique subset of literature that created paradigm shifts in vascular surgery. DS should be utilized as an adjunct to CC to avoid overlooking impactful research and influential researchers, and to measure true academic productivity.

Short-term Aronia melanocarpa extract supplementation improves cognitive performance: a randomized, double-blind, placebo-controlled cross-over study in healthy young adults.

PURPOSE: Evidence on the potential beneficial effects of anthocyanin-rich foods and supplements on cognitive performance is mainly based on acute or long-term studies in older adults. However, short-term studies focusing on a younger population are lacking. Therefore, short-term effects of Aronia melanocarpa extract (AME) supplementation on cognitive performance were investigated in healthy young adults. Potential underlying mechanisms were also addressed. METHODS: A randomized, double-blind, placebo-controlled cross-over study was performed involving 35 apparently healthy young adults. Participants consumed AME (180 mg anthocyanins/day) or a placebo for 1 week, separated by at least 2 weeks of wash-out. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Furthermore, arterial stiffness (carotid-to-femoral pulse wave velocity), retinal microvascular calibers (fundus photography), and serum brain-derived neurotrophic factor (BDNF) concentrations were measured at baseline and after 1 week. RESULTS: Participants had a mean age of 25 ± 4 years and an average BMI of 23.4 ± 2.7 kg/m2. Compliance was excellent and the study product was well-tolerated. As compared to placebo, movement time was significantly reduced by 4.8% within the five-choice reaction time test after 1 week of AME supplementation (intervention effect: - 12 ms; p < 0.05). Memory and executive function did however not change. Serum BDNF concentrations were significantly higher after AME supplementation as compared to placebo (+ 5.7%; intervention effect: 1.8 ng/mL; p < 0.05). However, arterial stiffness and retinal microvascular calibers were not affected. CONCLUSION: Short-term AME supplementation beneficially affected cognitive performance as attention and psychomotor speed improved. Serum BDNF concentrations were increased, but vascular function markers were not affected. CLINICAL TRIAL REGISTRATION: The study was registered on Clinical Trials under NCT03793777 on January 4th, 2019.

The efficacy of adjunctive mitomycin C and/or anti-VEGF agents on glaucoma tube shunt drainage device surgeries: a systematic review.

PURPOSE: The effectiveness of mitomycin C (MMC) in trabeculectomy has long been established. The aim of this review is to evaluate the efficacy and safety of adjunctive agents in tube shunt drainage device surgery for glaucoma or ocular hypertension, since controversy still exists regarding their benefit. METHODS: We searched CENTRAL, PubMed, Embase, Web of Science, Scopus, and BASE for RCTs, which have used adjuvant antimetabolites-either MMC or 5-Fluorouracil (5-FU)-and/or anti-vascular endothelial growth factors (anti-VEGF) agents. The main outcome was IOP reduction at 12 months. RESULTS: Ten studies met our inclusion criteria. Nine used the Ahmed Glaucoma Valve (AGV) implant, while the double-plate Molteno implant was used in one study. Four studies used MMC. The remaining six studies used an anti-VEGF drug - either bevacizumab, ranibizumab or conbercept. Only one MMC-study reported a significant difference in the IOP reduction between groups at 12 months, favouring the MMC group (55% and 51%; p < 0.01). A significant difference was also reported by two out of five bevacizumab-studies, both favouring the bevacizumab group (55% and 51%, p < 0.05; 58% and 27%, p < 0.05), with the highest benefit seen in neovascular glaucoma cases, especially when panretinal photocoagulation (PRP) was also used. Neither ranibizumab nor conbercept were found to produce significant differences between groups regarding IOP reduction. CONCLUSION: There is no high-quality evidence to support the use of MMC in tube shunt surgery. As for anti-VEGF agents, specifically bevacizumab, significant benefit seems to exist in neovascular glaucoma patients, especially if combined with PRP.

miR-210-5p Promotes Pulmonary Hypertension by Blocking ATP2A2.

AIM: Aberrant expression of ATPase sarcoplasmic/endoplasmic retic Ca2+ transporting 2 (ATP2A2) has attracted attention for its pathophysiologic role in pulmonary hypertension (PH). Several miRNAs, including miR-210-5p, have also been reported to be pathogenic factors in PH, but their exact mechanisms remain unknown. This study aimed to elucidate the potential mechanisms of miR-210-5p and ATP2A2 in MCT-induced PH. METHODS: Eighteen Sprague-Dawley rats were randomly divided into two groups-monoclonal (MCT) group and control group-and then administered MCT (60 mg/kg) and saline, respectively. mPAP, PVR, RVHI, WT%, and WA% were significantly increased in PH rats after 3 weeks, confirming that the modeling of PH rats was successful. Subsequently, we determined the expression of ATP2A2 and miR-210-5p in lung tissues using WB and qRT-PCR methods. We established an in vitro model using BMP4 and TGF-ß1 treatment of pulmonary artery smooth muscle cells (PASMCs) and examined the expression of ATP2A2 and miR-210-5p using the same method. To further elucidate the regulatory relationship between ATP2A2 and miR-210-5p, we altered the expression level of miR-210-5p and detected the corresponding changes in ATP2A2 levels. In addition, we demonstrated the relationship by dual luciferase experiments. Finally, the effect of silencing ATP2A2 could be confirmed by the level of cell membrane Ca2+ in PAMSCs. RESULTS: Up-regulation of miR-210-5p and down-regulation of ATP2A2 were observed in the MCT group compared with the control group, which was confirmed in the in vitro model. In addition, elevated miR-210-5p expression decreased the level of ATP2A2 while increasing the proliferation of PASMCs, and the results of the dual luciferase assay further confirmed that ATP2A2 is a downstream target of miR-210-5p. Additionally, silencing ATP2A2 resulted in increased cytoplasmic Ca2+ levels in PAMSCs. CONCLUSION: In MCT-induced PH, miR-210-5p promotes pulmonary vascular remodeling by inhibiting ATP2A2.

Pulmonary thrombotic pulmonary hypertension managed using antithrombotic and pulmonary vasodilator treatment.

An 8-year-old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution (Day 1). Treatment including oxygen, clopidogrel, and low-molecular-weight heparin was initiated for suspected pulmonary thrombosis. However, exertional dyspnea persisted until Day 10, and increased tricuspid regurgitation velocity, pulmonary vascular resistance, and McConnell's signs also were observed. Thus, beraprost sodium was administered PO on Day 11 to treat suspected pulmonary hypertension. On Day 13, contrast-enhanced computed tomography identified extensive contrast defects in the pulmonary arteries, and IV monteplase was administered on Days 14 and 18, with marked improvement in respiratory status and exertional dyspnea on Day 20. Right ventricular function and McConnell signs also improved, and tricuspid regurgitation velocity and pulmonary vascular resistance decreased. On Day 250, echocardiography indicated further improvement in pulmonary hypertension pathophysiology. The patient was still progressing well with antithrombotic and pulmonary vasodilator treatment 400 days later.

New insights into the roles of Irisin in diabetic cardiomyopathy and vascular diseases.

Diabetes mellitus (DM) is a prevalent chronic disease in the 21st century due to increased lifespan and unhealthy lifestyle choices. Extensive research indicates that exercise can play a significant role in regulating systemic metabolism by improving energy metabolism and mitigating various metabolic disorders, including DM. Irisin, a well-known exerkine, was initially reported to enhance energy expenditure by indicating the browning of white adipose tissue (WAT) through peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling. In this review, we summarize the potential mechanisms underlying the beneficial effects of Irisin on glucose dysmetabolism, including reducing gluconeogenesis, enhancing insulin energy expenditure, and promoting glycogenesis. Additionally, we highlight Irisin's potential to improve diabetic vascular diseases by stimulating nitric oxide (NO) production, reducing oxidative and nitrosative stress, curbing inflammation, and attenuating endothelial cell aging. Furthermore, we discuss the potential of Irisin to improve diabetic cardiomyopathy by preventing cardiomyocyte loss and reducing myocardial hypertrophy and fibrosis. Given Irisin's promising functions in managing diabetic cardiomyopathy and vascular diseases, targeting Irisin for therapeutic purposes could be a fruitful avenue for future research and clinical interventions.

Endothelial progenitor cells control remodeling of uterine spiral arteries for the establishment of utero-placental circulation.

Placental ischemia, resulting from inadequate remodeling of uterine spiral arteries, is a factor in the development of preeclampsia. However, the effect of endothelial progenitor cells that play a role in the vascular injury-repair program is largely unexplored during remodeling. Here, we observe that preeclampsia-afflicted uterine spiral arteries transition to a synthetic phenotype in vascular smooth muscle cells and characterize the regulatory axis in endothelial progenitor cells during remodeling in human decidua basalis. Excessive sEng, secreted by AMP-activated protein kinase (AMPK)-deficient endothelial progenitor cells through the inhibition of HO-1, damages residual endothelium and leads to the accumulation of extracellular matrix produced by vascular smooth muscle cells during remodeling, which is further confirmed by animal models. Collectively, our findings suggest that the impaired functionality of endothelial progenitor cells contributes to the narrowing of remodeled uterine spiral arteries, leading to reduced utero-placental perfusion. This mechanism holds promise in elucidating the pathogenesis of preeclampsia.

Are Barriers to Physical Activity Associated With Changing Physical Activity Levels and Sedentary Time in Patients With Peripheral Arterial Disease? A Longitudinal Study.

The aims of the current study were to analyze the association between the barriers to and changes in physical activity levels and sedentary behavior, as well as to examine whether these barriers change over time in patients with peripheral artery disease. In this longitudinal study, we assessed 72 patients (68% men; 65.7 ± 9.2 years). Physical activity was measured over a 7-day period using an accelerometer, and data were collected on time spent in sedentary activities, low-light physical activities, and moderate-to-vigorous physical activities. Personal and environmental barriers to physical activity were collected using yes or no questions. Assessments were repeated in the same patients after 27 months (95% confidence interval [26, 28] months). Most barriers remained stable in these patients; however, those who reported lack of money experienced an increase in sedentary behavior (ß = 392.9 [159.7] min/week, p = .02) and a decrease in low-light physical activity (ß = -372.4 [140.1] min/week, p = .02). These findings suggest that patients with symptomatic peripheral artery disease typically exhibit stable barriers over time, and individuals reporting lack of money demonstrated a decrease in low-light physical activity and an increase in sedentary behavior after 27 months.

FHL2 in arterial medial calcification in chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Arterial medial calcification (AMC) is a common complication in individuals with chronic kidney disease (CKD), which can lead to cardiovascular morbidity and mortality. The progression of AMC is controlled by a key transcription factor called runt-related transcription factor 2 (RUNX2), which induces vascular smooth muscle cells (VSMCs) transdifferentiation into a osteogenic phenotype. However, RUNX2 has not been targeted for therapy due to its essential role in bone development. The objective of our study was to discover a RUNX2 coactivator that is highly expressed in arterial VSMCs as a potential therapy for AMC. METHODS: We employed transcriptomic analysis of human data and an animal reporter system to pinpoint FHL2 as a potential target. Subsequently, we investigated the mRNA and protein expression patterns of FHL2 in the aortas of both human and animal subjects with CKD. To examine the role of FHL2 in the RUNX2 transcription machinery, we conducted coimmunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) experiments. Next, we manipulated FHL2 expression in cultured VSMCs to examine its impact on high phosphate-induced transdifferentiation. Finally, we employed FHL2 null mice to confirm the role of FHL2 in the development of AMC in vivo. RESULTS: Among all the potential RUNX2 cofactor, FHL2 displays selective expression within the cardiovascular system. In the context of CKD subjects, FHL2 undergoes upregulation and translocation from the cytosol to the nucleus of arterial VSMCs. Once in the nucleus, FHL2 interacts structurally and functionally with RUNX2, acting as a coactivator of RUNX2. Notably, the inhibition of FHL2 expression averts transdifferentiation of VSMCs into an osteogenic phenotype and mitigates aortic calcification in uremic animals, without causing any detrimental effects on the skeletal system. CONCLUSION: These observations provide evidence that FHL2 is a promising target for treating arterial calcification in patients with CKD.

Exploring the link between brain topological resilience and cognitive performance in the context of aging and vascular risk factors: A cross-ethnicity population-based study.

Brain aging is typically associated with a significant decline in cognitive performance. Vascular risk factors (VRF) and subsequent atherosclerosis (AS) play a major role in this process. Brain resilience reflects the brain's ability to withstand external perturbations, but the relationship of brain resilience with cognition during the aging process remains unclear. Here, we investigated how brain topological resilience (BTR) is associated with cognitive performance in the face of aging and vascular risk factors. We used data from two cross-ethnicity community cohorts, PolyvasculaR Evaluation for Cognitive Impairment and Vascular Events (PRECISE, n = 2220) and Sydney Memory and Ageing Study (MAS, n = 246). We conducted an attack simulation on brain structural networks based on k-shell decomposition and node degree centrality. BTR was defined based on changes in the size of the largest subgroup of the network during the simulation process. Subsequently, we explored the negative correlations of BTR with age, VRF, and AS, and its positive correlation with cognitive performance. Furthermore, using structural equation modeling (SEM), we constructed path models to analyze the directional dependencies among these variables, demonstrating that aging, AS, and VRF affect cognition by disrupting BTR. Our results also indicated the specificity of this metric, independent of brain volume. Overall, these findings underscore the supportive role of BTR on cognition during aging and highlight its potential application as an imaging marker for objective assessment of brain cognitive performance.

Is salvage Plug-Assisted Retrograde Transvenous Obliteration (PARTO) safe and effective for bleeding gastric varices ?- A preliminary single-center experience.

BACKGROUND: Vascular plug-assisted retrograde transvenous obliteration (PARTO) obliterates the gastric varices and portosystemic shunt, thus resulting in a lower rebleeding rate than endoscopic glue/sclerotherapy. AIMS: To evaluate the safety and efficacy of PARTO as salvage therapy in liver cirrhosis with gastric variceal bleed (GVB) after failed endotherapy. We assessed the clinical success rate and changes in liver function at 6- months. MATERIALS AND METHODS: Patients who underwent salvage PARTO after failed endotherapy for GVB (between December 2021 and November 2022) were searched and analyzed from the hospital database. Clinical success rate and rebleed rate were obtained at six months. Child-Pugh score (CTP) and Model for end-stage liver disease (MELD) score were calculated and compared between baseline and 6-month follow-up. RESULTS: Fourteen patients (n = 14, Child-Pugh class A/B) underwent salvage PARTO. Nine had GOV-2, and five had IGV-1 varices. The mean shunt diameter was 11.6 ± 1.6 mm. The clinical success rate of PARTO was 100% (no recurrent gastric variceal hemorrhage within six months). No significant deterioration in CTP (6.79 ± 0.98 vs. 6.21 ± 1.52; p = 0.12) and MELD scores (11.5 ± 4.05 vs. 10.21 ± 3.19; p = 0.36) was noted at 6 months. All patients were alive at 6 months. One patient (n = 1, 7.1%) bled from esophageal varices after three days of PARTO and was managed with variceal banding. 21.4% (3/14) patients had progression of esophageal varices at 6 months requiring prophylactic band ligation. Three patients (21.4%) had new onset or worsening ascites and responded to low-dose diuretics therapy. CONCLUSIONS: PARTO is a safe and effective procedure for bleeding gastric varices without any deterioration in liver function even after six months. Patient selection is critical to prevent complications. Further prospective studies with larger sample size are required to validate our findings.

BAG3 promotes proliferation and migration of arterial smooth muscle cells by regulating STAT3 phosphorylation in diabetic vascular remodeling.

BACKGROUND: Diabetic vascular remodeling is the most important pathological basis of diabetic cardiovascular complications. The accumulation of advanced glycation end products (AGEs) caused by elevated blood glucose promotes the proliferation and migration of vascular smooth muscle cells (VSMCs), leading to arterial wall thickening and ultimately vascular remodeling. Therefore, the excessive proliferation and migration of VSMCs is considered as an important therapeutic target for vascular remodeling in diabetes mellitus. However, due to the lack of breakthrough in experiments, there is currently no effective treatment for the excessive proliferation and migration of VSMCs in diabetic patients. Bcl-2-associated athanogene 3 (BAG3) protein is a multifunctional protein highly expressed in skeletal muscle and myocardium. Previous research has confirmed that BAG3 can not only regulate cell survival and apoptosis, but also affect cell proliferation and migration. Since the excessive proliferation and migration of VSMCs is an important pathogenesis of vascular remodeling in diabetes, the role of BAG3 in the excessive proliferation and migration of VSMCs and its molecular mechanism deserve further investigation. METHODS: In this study, BAG3 gene was manipulated in smooth muscle to acquire SM22αCre; BAG3FL/FL mice and streptozotocin (STZ) was used to simulate diabetes. Expression of proteins and aortic thickness of mice were detected by immunofluorescence, ultrasound and hematoxylin-eosin (HE) staining. Using human aorta smooth muscle cell line (HASMC), cell viability was measured by CCK-8 and proliferation was measured by colony formation experiment. Migration was detected by transwell, scratch experiments and Phalloidin staining. Western Blot was used to detect protein expression and Co-Immunoprecipitation (Co-IP) was used to detect protein interaction. RESULTS: In diabetic vascular remodeling, AGEs could promote the interaction between BAG3 and signal transducer and activator of transcription 3 (STAT3), leading to the enhanced interaction between STAT3 and Janus kinase 2 (JAK2) and reduced interaction between STAT3 and extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in accumulated p-STAT3(705) and reduced p-STAT3(727). Subsequently, the expression of matrix metallopeptidase 2 (MMP2) is upregulated, thus promoting the migration of VSMCs. CONCLUSIONS: BAG3 upregulates the expression of MMP2 by increasing p-STAT3(705) and decreasing p-STAT3(727) levels, thereby promoting vascular remodeling in diabetes. This provides a new orientation for the prevention and treatment of diabetic vascular remodeling.

Placental inflammation in a fetal demise of a SARS-CoV-2-asymptomatic, COVID-19-unvaccinated pregnant woman: a case-report.

BACKGROUND: Intrauterine fetal demise is a recognized complication of coronavirus disease 2019 in pregnant women and is associated with histopathological placental lesions. The pathological mechanism and virus-induced immune response in the placenta are not fully understood. A detailed description of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced inflammation in the placenta during fetal demise is crucial for improved clinical management. CASE PRESENTATION: We report the case of a 27-week gestation SARS-CoV-2-asymptomatic unvaccinated pregnant woman without comorbidities or other risk factors for negative pregnancy outcomes with a diagnosis of intrauterine fetal demise. Histopathological findings corresponded to patterns of subacute inflammation throughout the anatomic compartments of the placenta, showing severe chorioamnionitis, chronic villitis and deciduitis, accompanied by maternal and fetal vascular malperfusion. Our immunohistochemistry results revealed infiltration of CD68+ macrophages, CD56+ Natural Killer cells and scarce CD8+ T cytotoxic lymphocytes at the site of placental inflammation, with the SARS-CoV-2 nucleocapsid located in stromal cells of the chorion and chorionic villi, and in decidual cells. CONCLUSION: This case describes novel histopathological lesions of inflammation with infiltration of plasma cells, neutrophils, macrophages, and natural killer cells associated with malperfusion in the placenta of a SARS-CoV-2-infected asymptomatic woman with intrauterine fetal demise. A better understanding of the inflammatory effects exerted by SARS-CoV-2 in the placenta will enable strategies for better clinical management of pregnant women unvaccinated for SARS-CoV-2 to avoid fatal fetal outcomes during future transmission waves.

Congenital Intracranial Vascular Malformations in Children : Radiological Overview.

Prompt medical attention is crucial for congenital intracranial vascular malformations in children and newborns due to potential severe outcomes. Imaging is pivotal for accurate identification, given the diverse risks and treatment strategies. This article aims to enhance the identification and understanding of congenital intracranial vascular abnormalities including arteriovenous malformation, arteriovenous fistula, cavernous malformation, capillary telangiectasia, developmental venous anomaly, and sinus pericranii in pediatric patients.

Nonbacterial thrombotic endocarditis of mitral valve associated with a lymphoproliferative malignancy: case report and literature review.

BACKGROUND: Non-bacterial thrombotic endocarditis (NBTE) is a rare condition marked by sterile vegetations on cardiac valves, often linked to rheumatologic diseases, autoimmune disorders, and advanced solid malignancies. An early diagnosis and treatment of the associated clinical condition are mandatory, although they do not usually eliminate valvular vegetations, making anticoagulation essential to prevent embolic events. Despite variability, the prognosis of NBTE is usually unfavorable due to recurrent embolic events and the severity of the primary condition, typically advanced cancer. CASE PRESENTATION: We present a case of a 57 years-old male who presented to the emergency department with a 5-day history of painful bilateral digital edema and color change episodes (from pallor to cyanosis). Physical examination revealed erythrocyanosis in the distal extremities, prompting consideration of secondary Raynaud syndrome. Despite medical therapy, progressive digital ischemia led to multiple finger amputations. During etiological investigation, anticoagulation tests and autoimmune analysis yielded negative results. A transesophageal echocardiogram was performed, revealing an irregular hyperechogenic mass on the anterior leaflet of the mitral valve without valve dysfunction, and a thoracic computed tomography scan with contrast showed an enlarged right paratracheal lymph node. Histopathological analysis from a transthoracic needle biopsy of the paratracheal lymph node revealed diffuse large B-cell lymphoma. The patient underwent aggressive R-CHOP chemotherapy, achieving a favorable complete response. CONCLUSION: This is a particular case involving the occurrence of NBTE and Raynaud phenomenon as the initial paraneoplastic manifestations in a previously healthy young man. Reports of NBTE associated with lymphoproliferative conditions are quite rare, with fewer than ten cases described in the literature. To our knowledge, this is the first case of NBTE specifically associated with diffuse large B-cell lymphoma.

Non-surgical treatment of stage 4A retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants, often requiring surgical interventions in advanced stages. This retrospective case series study investigates non-surgical management for Stage 4A ROP, specifically the use of combined laser therapy and intravitreal anti-vascular endothelial growth factor (VEGF) injections. METHODS: Ten eyes from five infants with Stage 4A ROP were treated with a combined laser and anti-VEGF approach. Comprehensive follow-up examinations were conducted to evaluate the treatment outcomes. RESULTS: The study demonstrated successful retinal attachment without complications, showcasing the efficacy and safety of this non-surgical method. A comparison with surgical interventions highlighted the potential benefits in terms of reduced adverse effects. DISCUSSION: This combined treatment emerges as a promising first-choice option for Stage 4A ROP, offering rapid regression without surgical intervention, particularly in early stages. However, larger randomized clinical trials are necessary to validate these findings and establish definitive guidelines for managing this complex condition. CONCLUSION: Combined laser and anti-VEGF therapy proved to be an effective and safe non-surgical approach for Stage 4A ROP, with the potential to reduce the need for surgery, especially in its early presentation. Further research is required to confirm these findings and provide comprehensive recommendations for clinical practice.

Recurrent gastric antral vascular ectasia: a single center experience.

Introduction: Gastric antral vascular ectasia (GAVE) is a rare cause of chronic or acute gastrointestinal bleeding. This condition accounts for ∼4% of upper gastrointestinal bleeding cases. This disease is often associated with systemic diseases, such as liver cirrhosis, chronic kidney failure, autoimmune conditions, diabetes mellitus, hypothyroidism, and cardiovascular diseases. However, its etiopathogenesis remains controversial. Materials and method: We retrospectively reviewed the cases of GAVE treated at our digestive surgery unit. A total of nine patients were identified with a male/female ratio of 1.25:1 and an average age of 75.51 years (SD ± 9.85). All patients underwent endoscopic argon plasma coagulation (APC) treatment. At the time of the review, data on eight patients were available after 36 months of follow-up. Results: APC appears to be safe and effective for hemostasis of bleeding vascular ectasia. Only one (11.1%) patient required surgical intervention due to hemodynamic instability after multiple unsuccessful endoscopic treatments. No intraoperative and postoperative complication or bleeding relapse was experienced. Discussion: Based on our findings, we concluded that endoscopic APC is technically simple, but requires multiple re-interventions due to the incidence of relapses. Furthermore, larger randomized studies should be conducted to assess the role of elective surgery as the first intervention in stable patients with severe pathology and the timing of surgery after failed endoscopic treatment.