bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Success of Forest Land Based on Geographic Information Systems, in Wonosalam District, Jombang Regency
Authors: Maroeto  , Rossyda P. , Idhom Mohammad , Santoso Wahyu , Siswanto
Published: January 2023

The benefits of forests for life are not only for local communities living around forests, but also for global communities whose lives depend on forests as a resource that is able to provide various functions related to environmental management. The research aims to identify the potential of the Wonosalam forest area planned for UPN Integrated Farming & Forestry Tourism (UIFFT) - KHDTK Wonosalam in support of conservation policies by mapping forest areas based on land suitability characteristics and land availability suitable for KHDTK development. This type of research is survey research. and spatial analysis using Geographic Information Systems. Location in this research was conducted in the Wonosalam Forest Area in Wonosalam District. Wonosalam District is located in Jombang Regency with an area of 121.63 km2. The results of the study can be concluded that 1. the results of the survey of regional characteristics and physical and chemical analysis of the soil for durian, clove and coffee plants have land suitability classes that are actually in accordance with marginal (S3eh) with a limiting factor on erosion hazard while for potential after experiencing improvements that are not overall permanent value obtained is quite appropriate (S2) with various limiting factors but most of the constraints on erosion hazard and land preparation. 2. The direction of forest area development in future research areas based on land suitability is an integrated farming forestry area with a technological approach, and plant suitability so that this area can become a center for research, innovation, education, training, empowerment and community assistance without compromising its function. forests as environmental conservationists in an integrated manner.
Generation of various vortex beams based on transformation materials
Authors: Lai Yunyun , Dong Wenxiu , Hu Jin
Published: January 2023

A flexible vortex beam generator (VBG) is proposed based on transformation optics (TO) to convert input plane waves to various output vortex beams. The methodology is a geometrical one based on the topological equivalence between the vortex beam cross section disc and a belt, turning the in-plane curvilinear distributed phase or polarization structures in the disc to be redistributed around the belt. Consequently, abundant vortex beams can be exported by simply configuring the incidence angles and polarization directions of the plane waves. The topology and wave propagation characteristics behind the system are investigated, and TO is used to obtain the desired materials by adopting a specific space mapping. Some sample numerical simulations are described to verify the feasibility of the proposed design, including several complex orbital angular momentum and cylindrical vector beams. Due to its flexibility and simplicity, the proposed VBG is likely to have extensive application prospects.
313 Assessment of racial differences of atopic dermatitis characteristics in a diverse outpatient cohort in the United States
Authors: Sanfilippo Eric , Iyer Sneha , Patel Nisha , Silverberg Jonathan I
Published: January 2023

Atopic dermatitis (AD) can present differently across racial groups. To promote equality and consistency, dermatologists and other providers should properly recognize the heterogeneous manifestations of AD across racial groups. Yet, little is known about differences in how the commonly different features of AD occur by race. We assessed racial differences in the proportions of select key features of AD. The healthcare claims database from a large metropolitan tertiary care medical centre was queried for patients with physician-diagnosed AD using International Classification of Disease, Tenth Revision and Clinical Modification codes L20.x. Medical records were reviewed for demographics, comorbidities and documentation of Hanifin-Rajka criteria. The frequency of each criterion was evaluated by race (White, Black, Asian and Multiracial–Other). Overall, 766 patients with AD were included in the study; 374 (48.8%) were White, 284 (37.1%) Black, 89 (11.6%) Asian and 19 (2.5%) multiracial/other, 558 (68.2%) were female, 50 (6.1%) were age <18 years, 456 (55.7%) age 18–49 years and 313 (38.2%) age ≥50 years. Compared to White patients, Black patients had significantly higher proportions of personal (81.4% vs. 57.3%) and family (63.3% vs. 42.2%) history of atopic disease, perifollicular accentuation (60.6% vs. 36.9%) and xerosis on physical exam (84.2% vs. 73.9%)(P ≤ 0.03 for all). Multiracial/other patients had elevated proportions of a history of dry skin (81.3%), xerosis on physical exam (86.7%) and elevated Immunoglobulin E levels (75.0%). Black and multiracial/other patients had food hypersensitivity compared to White patients (50.0% and 71.4% vs. 35.1%, P = 0.04). There were marginally significant differences in the proportion of early-age AD onset (56.9% vs. 41.8%, P = 0.07) and anterior neck fold involvement (42.6% vs. 25.3%, P = 0.06) in Asian compared to White patients. There were no significant racial differences in the likelihood of other Hanifin-Rajka criteria, including pruritus, flexural dermatitis, chronic dermatitis, ichthyosis, nipple eczema, hand/foot dermatitis, immediate skin reactivity, subcapsular cataracts, cutaneous infections, pruritus when sweating, intolerance to wool/lipid solvents, environmental/emotional factors worsening AD, or white dermatographism. Our results suggest there are racial differences in AD characteristics even within a single region. These differences may be attributable to population-differences in genetics, environmental exposures, skincare practices etc. Future research is needed to understand the mechanisms and treatment responses of these heterogeneous AD presentations.
336 Efficacy of dupilumab in infants and preschoolers with atopic dermatitis up to 1 year
Authors: Paller Amy S , Siegfried Elaine C , Xiao Jing , Prescilla Randy , Bansal Ashish
Published: January 2023

Continuous use of several traditional systemic atopic dermatitis (AD) treatments in pediatric patients is not recommended due to safety concerns and lack of long-term efficacy data. Children aged 6 months to 5 years with moderate-to-severe AD who had participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434, part B; parent study) were enrolled in an open-label extension (OLE) study (NCT02612454). Patients received subcutaneous dupilumab every 4 weeks (200 mg for children weighing 5 to <15 kg; 300 mg for 15 to <30 kg). Topical AD treatments were allowed. Relative to the parent study baseline, mean percentage changes (± standard error) in Eczema Area and Severity Index score were −41.6 (±4.6) and −54.0 (±3.2) at OLE baseline, −74.5 (±3.7) and −81.7 (±1.8) at week 16, and −85.6 (±3.5) and −86.4 (±2.2) at week 52 in the 200 and 300 mg dupilumab groups, respectively. The number of patients (%) achieving an Investigator’s Global Assessment score of 0/1 increased from OLE baseline (6/61 [9.8%] and 15/116 [12.9%]) to week 16 (22/58 [37.9%] and 35/115 [30.4%]), and at week 52 (16/34 [47.1%] and 18/54 [33.3%]) in the 200 and 300 mg dupilumab groups, respectively. The overall safety of dupilumab treatment administered for up to 1 year was consistent with the known dupilumab safety profile. Dupilumab treatment for 1 year provides sustained improvement in signs of AD in patients aged 6 months to 5 years with moderate-to-severe AD.
The motor system is exceptionally vulnerable to absence of the ubiquitously expressed superoxide dismutase-1
Authors: Park Julien H , Nordström Ulrika , Tsiakas Konstantinos , Keskin Isil , Elpers Christiane , Mannil Manoj , Heller Raoul , Nolan Melinda , Alburaiky Salam , Zetterström Per , Hempel Maja , Schara-Schmidt Ulrike , Biskup Saskia , Steinacker Petra , Otto Markus , Weishaupt Jochen , Hahn Andreas , Santer René , Marquardt Thorsten , Marklund Stefan L , Andersen Peter M
Published: January 2023

Superoxide dismutase-1 is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 can cause amyotrophic lateral sclerosis, probably via a toxic gain-of-function involving protein aggregation and prion-like mechanisms. Recently, homozygosity for loss-of-function mutations in SOD1 has been reported in patients presenting with infantile-onset motor neuron disease. We explored the bodily effects of superoxide dismutase-1 enzymatic deficiency in eight children homozygous for the p.C112Wfs*11 truncating mutation. In addition to physical and imaging examinations, we collected blood, urine and skin fibroblast samples. We used a comprehensive panel of clinically established analyses to assess organ function and analysed oxidative stress markers, antioxidant compounds, and the characteristics of the mutant Superoxide dismutase-1. From around 8 months of age, all patients exhibited progressive signs of both upper and lower motor neuron dysfunction, cerebellar, brain stem, and frontal lobe atrophy and elevated plasma neurofilament concentration indicating ongoing axonal damage. The disease progression seemed to slow down over the following years. The p.C112Wfs*11 gene product is unstable, rapidly degraded and no aggregates were found in fibroblast. Most laboratory tests indicated normal organ integrity and only a few modest deviations were found. The patients displayed anaemia with shortened survival of erythrocytes containing decreased levels of reduced glutathione. A variety of other antioxidants and oxidant damage markers were within normal range. In conclusion, non-neuronal organs in humans show a remarkable tolerance to absence of Superoxide dismutase-1 enzymatic activity. The study highlights the enigmatic specific vulnerability of the motor system to both gain-of-function mutations in SOD1 and loss of the enzyme as in the here depicted infantile superoxide dismutase-1 deficiency syndrome.
The impacts of hypoxia-inducible factor stabilizers on laboratory parameters and clinical outcomes in chronic kidney disease patients with renal anemia: a systematic review and meta-analysis
Authors: Takkavatakarn Kullaya , Thammathiwat Theerachai , Phannajit Jeerath , Katavetin Pisut , Praditpornsilpa Kearkiat , Eiam-Ong Somchai , Susantitaphong Paweena
Published: January 2023

Renal anemia in chronic kidney disease (CKD) is associated with poor outcomes. Hypoxia-inducible factor (HIF) stabilizer, which induces endogenous erythropoietin synthesis and enhances iron mobilization, is a novel treatment for anemia in CKD. We conducted a systematic review and meta-analysis to analyze the effect of HIF stabilizers in anemic CKD patients. This meta-analysis included 43 officially published articles and 3 unpublished studies (27 338 patients). HIF stabilizer treatment significantly increased hemoglobin (Hb) level when compared with placebo (mean difference 1.19 g/dL; 95% confidence interval 0.94 to 1.44 g/dL; P < .001). There was no significant difference in Hb level when compared with erythropoiesis-stimulating agents (ESAs). Significant reductions of ferritin and transferrin saturation (TSAT) were observed, while total iron-binding capacity was increased in the HIF stabilizer group compared with placebo or ESAs. HIF stabilizers significantly reduced hepcidin, high-density lipoprotein, low-density lipoprotein and triglyceride levels. Acute kidney injury and thrombotic events were significantly observed in patients receiving HIF stabilizers. There were no significant differences in myocardial infarction, stroke, dialysis initiation, pulmonary hypertension and mortality between HIF stabilizer and control groups. The present meta-analysis provided evidence that HIF stabilizers increased Hb and TIBC levels and reduced hepcidin, ferritin and TSAT in CKD patients with renal anemia. Long-term follow-up studies on clinical outcomes of HIF stabilizers are still needed.
Long-term results of zero-fluoroscopy catheter ablation in pregnant patients with arrhythmias: a 2-year follow-up study
Authors: Abdrakhmanov A , Ainabekova B , Nuralinov O , Smagulova A
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Incidences of rhythm disturbance in pregnant are commonly seen. Catheter ablation of arrhythmias has been shown to be effective and safe. Data on perinatal outcomes and results of zero-fluoroscopy catheter ablation in pregnant patients is limited.

Purpose

the aim of our study is to observe long-term results and perinatal outcomes in pregnant women with arrhythmias, treated by zero-fluoroscopy catheter ablation method.

Methods

There were 48 pregnant women, who underwent zero-fluoroscopy catheter ablation (Mean age of pregnant was 25.7±4.3 years, mean gestation age 24.1 ±3.2 weeks). Procedure-related complications, perinatal outcomes and arrhythmia recurrence were documented during 24 months follow-up.

Results

The most common arrhythmias were atrioventricular nodal reentrant tachycardia (n=21; 43.75%). This was followed by Wolff–Parkinson–White syndrome (n=15; 31.25%). Combination of accessory pathways with slow conduction ways were found in 3 cases (6.25%). In six cases were ablation due to frequent premature ventricular contraction (12.5%). Ventricular tachycardia was rare during pregnancy (n=3; 6.25%). Zero-fluoroscopy catheter ablation was performed under the guidance of CARTO (n=21; 43.75%) and Ensite Precision systems (n=27; 56.25%). The median procedural time was 71±15 minutes. Interventions were effective in all cases (100%). Procedural complication was in one patient (2.1%), who developed an ileofemoral thrombosis. Pregnancy course after ablation procedure was benign in all patients. Perinatal outcomes: spontaneus vaginal delivery was in the majority of cases (n=36; 75%). Twelve pregnancies (25%) were delivered by cesarean section due to obstetric indicators. Intrapartum hemorrhage was 335.2±228.92 ml. Two women had placental abraption and preeclampsia (4.2%). Maternal adverse cardiac events were none declared. There were 48 live births (in all cases). Fetal birth weight was 3324.7±684.4 grams, 5 minute Apgar was 8.4±1.3. There were no maternal and fetal mortality. At 24 months there were no arrhythmia recurrence.

Conclusions

Zero-fluoroscopy catheter ablation method is safe and effective in pregnant women with arrhythmias. Pregnancy course and outcomes after this procedure is bening in the majority of cases.
Association between triglyceride and all-cause mortality and cardiovascular outcomes in heart failure patients: a territory-wide study in Hong Kong
Authors: Ren Q W , Tse Y K , Yiu K H
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Objectives

To determine the association between levels of triglyceride (TG) and all-cause mortality and cardiovascular outcomes. To evaluate the concentration of TG associated with the lower range and lowest risk of adverse outcomes in heart failure (HF) patients.

Methods

Using a previously validated territory-wide clinical information registry, all eligible patients with HF (N=147 396) from 1996 to 2020 were enrolled. Levels of time-weighted TG associated with risk of mortality were evaluated on a continuous scale using restricted cubic spline curves and by categories of TG with Cox proportional hazards regression model. The primary outcomes were all-cause mortality and cardiovascular death (CVD). Secondary outcomes include cause-specific mortality and incident cardiovascular events.

Results

Among 147 396 HF patients, the mean age was 70.0±12.5 years and 73 571 (49.9%) were male. The association between levels of time-weighted TG and the risk of all-cause mortality was J-shaped, with low and high levels associated with an increased risk of all-cause mortality, CVD and cause-specific mortality. Compared with individuals with levels of TG between 1.14 to 2.85 mmol/L, the multivariable-adjusted hazard ratio (HR) for all-cause mortality was 1.39 (95% confidence interval [CI] 1.35 to 1.44) for individuals with TG concentrations of less than 0.71 mmol/L and 1.97 (95% CI, 1.67 to 2.32) for TG concentrations of more than 5.60 mmol/L. The concentration of TG associated with the lowest risk of all-cause mortality was 1.84 mmol/L. Similar results were seen in males and females, in patients with or without lipid-lowering treatment, and for cardiovascular events.

Conclusion

In the HF population, low and high levels of TG were associated with an increased risk of all-cause mortality and cardiovascular outcomes. The lowest risk of all-cause mortality was found at a TG concentration of 1.84 mmol/L.
Factors Associated with Coronary Artery Calcification and Cardiovascular Outcome Among Pre-Dialysis Chronic Kidney Disease Patients in Phramongkutklao hospital
Authors: Anantawong V , Prasitdumrong H , Prasitdumrong H
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD) patients. Calcified coronary artery is highly prevalent and more severe among these group. Coronary calcium score was used as a risk predictor for coronary heart disease in general population but data among CKD patients were less known.

Objective

To evaluate factors associated with coronary calcium score in pre-dialysis CKD patients.

Methods

Prospective cohort study was conducted in CKD patients who have intermediate risk for coronary heart disease between February 2021 and December 2021. Patients who had received dialysis or coronary revascularization were excluded. GFR was categorized into 4 groups including Group 1: GFR ≥ 60 ml/min/1.73m2, Group 2: GFR 45-59 ml/min/1.73m2, Group 3: GFR 30-44 ml/min/1.73m2 and Group 4: GFR < 30 ml/min/1.73m2. Baseline geographical data and prespecified factors that might be correlated with coronary calcium score were collected and Agaston coronary calcium score was performed by 640-slice CT scanner with standard protocol. Primary outcome was evaluation of factors associated with coronary calcium score. Secondary outcome was incidence of composited cardiovascular events which defined as death, MI or heart failure within 6 months after enrollment.

Results

Total 53 males and 35 females were enrolled. Patients in Group 1, 2, 3 and 4 were 22, 24, 21 and 21 patients, respectively. Mean age, underlying hypertension, T2DM with target organ damage, PTH, ESR, Osteocalcin and coronary calcium score were significantly different between each group of GFR. Coronary calcium score showed inversely correlation with GFR level, p-value < 0.001. Factors that significantly correlated with coronary calcium score were mean age (r=0.548, p-value <0.001), underlying hypertension (r=0.466, p-value <0.001), CAVI (r=0.436, p-value <0.001) and Osteocalcin (r=0.83, p <0.001). In multivariate analysis, Osteocalcin was significantly correlated with coronary calcium score, p-value < 0.001. Increasing Osteocalcin 1 ng/ml correlated with increasing coronary calcium score 52, p-value < 0.001. Composited cardiovascular events were found in 11 patients, 6 patients in Group 3, and was not demonstrated correlation with coronary calcium score.

Conclusions

Coronary calcium score showed inversely correlation with GFR level. Increasing Osteocalcin was significantly correlated with increasing coronary calcium score in pre-dialysis CKD patients.
Novel serum biomarkers for predicting prognosis in post cardiac arrest patients
Authors: Song H
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Objective

To determine the clinical feasibility of novel serum biomarkers by comparing them with conventional serum biomarkers in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM).

Methods

This study was a prospective observational study conducted on OHCA patients who underwent TTM. We measured serum biomarker Neuron‑Specific Enolase (NSE), S-100B (S100 calcium-binding protein), Tau protein, Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NFL), and Ubiquitin C-terminal hydrolase-L1 (UCH-L1) at 0, 24, 48, and 72 hours after return of spontaneous circulation (ROSC). Conventional biomarkers include NSE and S-100B. The primary outcome was good neurologic outcome at 6 months after OHCA.

Results

A total of 100 patients were included in this study from August 2018 to May 2020. Among the included patients, 46 patients had good neurologic outcomes. As for the biomarker's AUC value measured immediately after ROSC, GFAP had the highest value (0.850), and among the values measured 24 hours after ROSC, S100B showed the highest value (0.901). The AUC values of biomarkers measured after 48 hours and 72 hours after ROSC, were the highest in NFL (0.921, 0.946). AUC values measured after 72 hours of ROSC showed higher values in novel biomarkers than in conventional biomarkers.

Conclusion

After 72 hours of ROSC, the Novel biomarkers showed a higher AUC value than the conventional biomarkers. Among them, NFL showed the highest AUC values than other biomarkers at 48 and 72 hours of ROSC.
Different cellular landscape of four types of non-diseased cardiac valves contributes to their differences in susceptibility of pathological remodeling and disease
Authors: Shu S , Fu M , Chen X , Song J
Published: January 2023

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): National Natural Science Foundation of China

Background

Exploring the mechanisms of valvular heart disease (VHD) at the cellular level may be useful to identify new therapeutic targets; however, the comprehensive cellular landscape of non-diseased human cardiac valve leaflets remains unclear.

Methods

The cellular landscapes of non-diseased human cardiac valve leaflets (five aortic valves, five pulmonary valves, five tricuspid valves, and three mitral valves) from end-stage heart failure patients undergoing heart transplantation were explored using single-cell RNA sequencing (scRNA-seq). Bioinformatics was used to identify the cell types, describe the cell functions, and investigate cellular developmental trajectories and interactions. Differences among the four types of cardiac valve at the cellular level were summarized. Pathological staining was performed to validate the key findings of scRNA-seq. An integrative analysis of our single-cell data and published genome-wide association study-based and bulk RNA sequencing-based data provided insights into the cell-specific contributions to calcific aortic valve diseases.

Results

Six cell types were identified among 128,412 cells from non-diseased human cardiac valve leaflets. Valvular interstitial cells were the largest population, followed by myeloid cells, lymphocytes, valvular endothelial cells, mast cells, and myofibroblasts. The four types of cardiac valve had distinct cellular compositions. The intercellular communication analysis revealed that valvular interstitial cells were at the center of the communication network. The integrative analysis of our scRNA-seq data revealed key cellular subpopulations involved in the pathogenesis of calcific aortic valve diseases.

Conclusions

The cellular landscape differed among the four types of non-diseased cardiac valve, which might explain their differences in susceptibility to pathological remodeling and VHD.
A canadian retrospective multicenter experience with selexipag in a heterogeneous group of pediatric pulmonary hypertension patients
Authors: Youssef D , Richards S , Lague S , Sheppard C , Smith J , Vorihes E , Hosking M , Pietrosanu M , Bates A
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

The introduction of the oral prostanoid selexipag for treating severe adult pulmonary arterial hypertension (PH) has contributed to reduced rates of death and secondary complications in PAH. Pediatric physicians have extrapolated from the adult literature to utilize this medication to treat severe pediatric pulmonary hypertension. However, longitudinal, multicenter data on the therapeutic benefits of selexipag for pediatric patients is lacking.

Materials and Methods

We performed a retrospective review describing the clinical outcomes of pediatric PH patients receiving selexipag for pulmonary hypertension (PH) therapy in addition to standard pulmonary vasodilator therapy across three North American pediatric PH centers between January 2005 and June 2021.

Results

Across three Canadian centers, 24 patients (15 female) with a mean age at diagnosis of 5.4 (0.9) years were included. Of this cohort, 19 (79.2%) had group 1 PAH, 4 (16.7%) had group 3 PH, and 1 (4.2%) had group 4 PH. Genetic syndromes were noted in 7 (29.2%) patients. Dosing was targeted to achieve 20–30 mcg/kg/dose orally every 12 hours; the mean dosage after 12 months was 31.2 (10.3) mcg/kg/dose. Twelve months following selexipag initiation, a median increase of 71.5 m (p = 0.44) in six-minute walk test distance was observed together with median decreases of 0.2 cm (p = 0.17) in tricuspid annular plane systolic excursion, 3.5 mmHg (p = 0.95) in right ventricle systolic pressure, and 6.1 mmHg (p = 0.09) in mean pulmonary artery pressure. 2 patients (8.3%) died, 1 (4.2%) was referred for a heart transplant, and 1 (4.2%) received an atrial flow regulator. One patient (4.2%) required admission to a pediatric intensive care unit during their treatment course this was related to profound desaturation, six (25.0%) had gastrointestinal symptoms, and two (8.3%) had facial flushing.

Conclusion

Selexipag appears to be a beneficial adjunctive therapy for selected pediatric PH patients and has a tolerable adverse effect profile aside from gastrointestinal disturbances. Further prospective studies of changes in hemodynamics and functional classification over a longer period and with a larger sample are needed.
Safety and efficacy of cerebral embolic protection devices in transcatheter aortic valve implantation: a meta-analysis
Authors: Tan N , Gao F , Mohammed R A , Lim S T , Abdul Aziz Z , Govindasamy S , Chao V T T , Ewe S H , Ho K W , Yap J
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Stroke during Transcatheter Aortic Valve implantation (TAVI) is not an uncommon complication with potential devastating consequences. With the extension of TAVI to the low-risk patient, stroke prevention takes on increasing importance. The use of cerebral embolic protection device (EPD) reveals conflicting data. This meta-analysis aims to evaluate the clinical efficacy and safety of EPDs.

Methods

A comprehensive literature search for all studies till May 2022 reporting clinical safety and efficacy outcomes of the only EPD approved for use by the Food and Drug Administration (FDA) was performed. Study outcomes were divided based on time period - overall (up to 30 days and in-hospital) and short (﻿≤7 days). Primary outcome was stroke - major and minor. Secondary outcomes included transient ischaemic attack (TIA), mortality, acute kidney injury (AKI), major vascular and bleeding complications.

Results

A total of 12 studies involving 288531 patients were analysed, which included 3 randomised controlled trials (RCTs), 7 propensity-matched and 2 cohort studies. Regarding overall outcomes, significant differences were noted for mortality (OR 0.59 [0.42-0.84], p=0.0036) and major stroke (OR 0.40 [0.18-0.91], p=0.028) (Fig 1). No significant differences were noted for all stroke (p=0.058), minor stroke (p=0.32), TIA (p=0.49), AKI (p=0.17), major vascular complications (p=0.40) and major bleeding complications (p=0.11). There was significant heterogeneity across the studies for mortality (p=0.032) and all stroke (p=0.009). In the subgroup analysis of studies reporting ﻿≤7 days outcomes (n=5), EPDs showed significantly lower rates of all stroke (0.33 [95% CI 0.19-0.56], p=<0.0001), major stroke (0.19 [0.08-0.48], p=0.0004) and major bleeding complications (OR 0.29 [0.10-0.79], p=0.016), but no significant differences for mortality (p=0.67) and minor stroke (p=0.070). There was no significant heterogeneity across the studies (all p>0.05)

Conclusions

In this meta-analysis including non-randomised studies, the use of EPDs was associated with lower mortality and major stroke rates, although significant heterogeneity was noted for the studies reporting mortality. Further ongoing larger scale RCTs will further clarify these results.
Understanding the management of hypertension in Asia: results of a literature search
Authors: Rahman A R , Magno J D A , Cai J , Han M , Lee H Y , Nair T , Narayan O , Panyapat J , Van Minh H , Khurana R
Published: January 2023

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Servier, France

Background

Hypertension poses a significant healthcare burden in Asia. Detection, treatment and control of hypertension are suboptimal, despite the existence of clear international guidelines and the availability of safe and effective treatments.

Purpose

To understand hypertension management in Asia, based on the analysis of national guidelines, treatment patterns and patient characteristics.

Methods

A PubMed search was performed using four search strings relating to 1) hypertension; 2) treatment/management/drug therapy; 3) guideline, consensus, real world evidence; and 4) Asian countries. The search was restricted to English language articles published since January 2008 to July 2022. Articles were filtered by relevance to the research question, study size, scope, methodology, and country/region to identify a target of 100 final references.

Results

The search yielded 2,436 articles, of which 92 were selected as being most relevant. Compared with Europeans, Asians appeared to have higher systolic blood pressure (BP), diastolic BP, and mean arterial pressure, with stronger association between BP and stroke. Rates of severe hypertension were also higher. Trends identified in the literature suggested that calcium channel blockers are the most common monotherapy used in Asian countries, with a high variability across the region. In the available publications focused on the studies with RAAS inhibitors, the majority of them compared the use of angiotensin receptor blockers as mono/combination therapy versus combination therapy with ACE inhibitors, calcium channel blockers or diuretics. Among treated patients, the observed control rates were only ~35–40% (~10% or less in the general population). There is a lack of focus on selecting the most appropriate treatment for each individual patient. Areas for improvement in delivering guideline-directed therapy for improved BP control also included facilitating access to health care and compliance with medication (including support mechanisms like community programmes, telemedicine, mobile phone apps and home BP monitoring), improving diet (reducing salt intake) and encouraging exercise.

Conclusions

Asian patients and European patients have different clinical profiles, with more severe hypertension in Asians. Rates of BP control across Asia are low. The management of hypertension requires a focused multimodal and supportive approach with implementation of public health measures, more effective screening initiatives and evidence-based goal-driven recommendations for appropriate pharmacotherapy augmented by lifestyle changes.
Association between non-alcoholic fatty liver disease and incidence of arrhythmia and other cardiovascular outcomes: a systematic review and meta-analysis
Authors: Jaiswal V I K A S H , Ang S O N G P , Hameed M A H A , Momi N K , Shah M A I T R I , Kanakannavar S S , Rajak K R I P A , Kalra K R I T I , Chia J I A E E , Wajid Z , Roy S , Agrawal V I B H O R , Sharma P R A C H I , Jaiswal A K A S H
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

The association between non-alcoholic fatty liver disease (NAFLD) with cardiovascular and cerebrovascular outcomes, as well as their clinical impact, has yet to be established in the literature.

Objective

We aim to evaluate the association between NAFLD patients and the risk of atrial fibrillation (AF), heart failure (HF),stroke, cardiovascular mortality (CVM), and peripheral revascularization.

Method

We performed a systematic literature search using the PubMed, Embase, Scopus, and Cochrane libraries for relevant articles from inception until July 20th, 2022. Odds ratios (OR) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant.

Results

A total of 10 studies with 17886340 patients (2887214 NAFLD vs 14999126 non-NAFLD) were included in our analysis. The average age and percentage of males were comparable between groups, with a mean age of 55 years and 72.5% of males in the NAFLD group, whereas 52 years and 47.4% of males in the non-NAFLD group. The most common comorbidities among the NAFLD group included: hypertension (38% vs 24%), diabetes mellitus (14% vs 8%). The mean follow-up duration was 6.26 years. The likelihood of atrial fibrillation [OR, 1.42(95%CI: 1.18-1.70), P<0.001], heart failure [OR, 1.48(95%CI: 1.27-1.73), P<0.001], stroke (OR, 1.26(95%CI: 1.17-1.36), P<0.001], and peripheral revascularization (OR, 3.95(95%CI: 1.60-9.73), P=0.003] was significantly higher in NAFLD patients when compared with non-NAFLD patients. In contrast, cardiovascular mortality was comparable between both the groups of patients [OR, 3.11(95%CI: 0.32-30.03), P=0.33] respectively.

Conclusion

Patients with NAFLD demonstrated increased incidence of cardiovascular and/or cerebrovascular outcomes; heart failure, stroke, and arrhythmia. Patients with associated comorbidities were at higher risk of cardiovascular disease, implying a greater need for screening and adoption of cardio-protective measures amongst NAFLD patients.
Prevalence of cardiovascular disease and thromboembolic events in a prospective cohort of patients with sickle cell disease
Authors: Natarajan N , Al-Mohammad A A , Robinson G R , Pillai R P , Tsitsikas D T , Ang R A
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

Sickle cell disease (SCD) is an inherited disorder of globin chains that cause haemolysis, thrombosis and chronic organ damage. SCD affects multiple organs including the cardiovascular system. The two main subtypes of SCD are the homozygous HbSS and the heterozygous HbSC form. Here we describe and compare the prevalence of cardiovascular disease and thromboembolic events between HbSS and HbSC forms of SCD.

Methods

This is an observational study where a prospective database of SCD patients from a UK centre was retrospectively analysed.

Results

A total of 291 patients were included from the database with 183 (63%) HbSS patients. HbSS patients were younger (40.8±11 vs 48.1±14, p=0.03) with more males (49% v 35%, p=0.02) compared to the HbSC group.

As expected, HbSS patients had more severe form of the disease with higher rate of hospital admissions for sickle related crises, transfusion related iron overload, and are more likely to be on prophylactic phenoxymethylpenicillin as well as disease modifying treatments (Table 1).

Cardiovascular risk factors hypertension and hypercholesterolemia were less prevalent in HbSS compared to HbSC patients. Interestingly, the prevalence of ischaemic heart disease and vascular disease is similarly low in both groups at around 1%. However, the prevalence of thromboembolic events, pulmonary hypertension and stroke/TIA is higher at between 4 to 8% with no significant difference between the groups (Table 2).

Conclusion

The different prevalence of cardiovascular risk factors between HbSS and HbSC may be explained by the difference in age between the groups. SCD would appear to have a differential effect on the cerebral, cardiac, pulmonary and peripheral circulations.
Perindopril Reduce SARS-COV-2 Spike-ACE2 Binding, ACE2 Overexpression and Cytokine Storm in Adipocyte Cell Infected with SARS-COV-2
Authors: Makhyan Jibril Al Farabi M J , Hanestya Oky Hermawan H O , Primasitha Maharani Harsoyo P M H , Stavros George Drakos S G D , I Gde Rurus Suryawan I G R , Meity Ardiana M A
Published: January 2023

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): Ristekdikti

Background and Aims

The SARS-CoV-2 virus can infect adipocyte cells via ACE2 Receptor thus triggering ACE2 overexpression and cytokine storms which cause lethal complications. Hence, we explore the effect of Perindopril on the expression of ACE2, IL-6, IL-1B TNF-α in adipocyte cultures infected by SARS-CoV-2 spike protein and identify the possible mechanism involved.

Materials and Methods

Adipocyte culture obtained from a healthy and obese donor was divided into 4 triplicate groups (P0: negative control without treatment; P1: positive control (SARS-CoV-2 spike protein); P2: SARS-CoV-2 spike protein + exposure to Perindopril 0.5 µM); P3: SARS-CoV-2 spike protein + anti-ACE2 antibody 100 µg/mL; and evaluated at 24 and 48 hours. ACE2 expression was evaluated using immunofluorescence. IL-6, TNFα, and IL-1B were evaluated using ELISA. SARS-COV-2 Spike-ACE2 Binding was evaluated using Competitive ELISA. Data analysis was performed using SPSS 25.0 software.

Results

At first 24 hours of incubation, perindopril treatment has the highest ACE2 expression compared to negative control, positive control and anti-ACE2 antibody (113.52±0.34 ng/mL vs 13.3±0.87 ng/mL, 90.2±2.73 ng/mL, 17.3±0.11 ng/mL, p<0.01), lower ACE-ACE2R binding compared to anti-ACE2 antibody group (169.52±4.07 ng/mL vs 290.71±6.22 ng/mL, p<0.01) and higher IL-6 expression compared to positive control group (64.65±0.12 ng/mL vs 60.08±0.77 ng/mL p<0.01). Interestingly, after 48 hours, perindopril treatment was shown to prevent further increase of ACE2 expression compared to a positive control (47.37±0.76 ng/mL vs 80.31±5.37 ng/mL, p<0.01), higher SARS-COV-2 Spike-ACE2 binding compared to anti-ACE2 antibody group (143.68±3.68 ng/mL vs 103.1±9.49 ng/mL, p<0.01), and lower IL-6 expression compared to the positive control group (42.66±1.94 ng/mL vs 90.93±2.48 ng/mL p<0.01). However, no significant difference in TNFα and IL-1B expression between perindopril treatment and positive control in both 24 and 48 hours.

Conclusion

This study showed that perindopril reduces cytokine storm by preventing ACE-2 and IL-6 overexpression via an increasing number of SARS-COV-2 Spike-ACE2 competitive binding in adipocyte culture infected with SARS-COV-2 spike protein. A further clinical trial is needed to prove the benefit of perindopril in obese patients with COVID-19.
Global burden of metabolic diseases: data from Global Burden of Disease 2000-2019. A cosortium of metabolic disease
Authors: Chew N , Ng C H , Tan D , Kong G , Lin C X , Chin Y H , Foo R , Chan M , Muthiah M
Published: January 2023

Funding Acknowledgements

Type of funding sources: None.

Background

The growing prevalence of metabolic diseases is a major concern. We sought to examine the global trends and mortality of metabolic diseases using estimates from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019.

Methods

Global estimates of prevalence, deaths, and disability-adjusted life year (DALYs) from 2000-2019 were examined for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, and nonalcoholic fatty liver disease [NAFLD]). For metabolic risk factors (hyperlipidemia and obesity), estimates were limited to mortality and DALYs. Death rates was compared across sex, World Health Organisation regions and Socio-demographic Index (SDI) quintiles. Age-standardised prevalence and death rates were presented per 100,000 population with 95% uncertainty intervals (UI).

Findings

From 2000 to 2019, prevalence rates increased for all metabolic diseases, with the most pronounced increase in high SDI countries. In 2019, the mean (95%UI) age-standardised prevalence per 100,000 population was estimated to be 15,023 (13,493-16,764) for NAFLD, 5,283 (4,864–5,720) for T2DM and 234 (171-313) for hypertension. The highest age-standardised death rates were observed in obesity (62·59 [39·92-89·13]; males, 66·55 [39·76-97·21]; females. 58·14 [38·53-81·39]), followed by hyperlipidemia (56·51 [41·83-73·62]; males, 67·33 [50·78-86·43]; females, 46·50 [32·70-62·38]), T2DM (18·49 [17·18-19·66], males, 67·33 [50·78-86·43]; females, 46·50 [32·70-62·38]), hypertension (15·16 [11·20-16·75]; males, 14·95 [10·32-16·75]; females, 15·05 [11·51-17·09]) and NAFLD (2·09 [1·61-2·60]; males, 2·38 [1·82-3·02]; females, 1·82 [1·41-2·27]). Mortality rates decreased over time in hyperlipidemia (-154%), hypertension (-52%) and NAFLD (-52%), but not in T2DM and obesity. The highest mortality for metabolic diseases was found in Eastern Mediterranean, and low to low-middle SDI countries.

Conclusion

The global prevalence of metabolic diseases has risen over the past two decades regardless of SDI. Attention is needed to address the unchanging mortality rates attributed to metabolic disease and the regional, socioeconomic, and sex disparities in mortality from metabolic disease.
The use of evidence-based medical therapy in patients with critical limb-threatening ischaemia
Authors: Bager Lucas Grove Vejlstrup , Petersen Jeppe Kofoed , Havers-Borgersen Eva , Resch Timothy , Smolderen Kim G , Mena-Hurtado Carlos , Eiberg Jonas , Køber Lars , Fosbøl Emil Loldrup
Published: January 2023

Aims

To describe the practice patterns of evidence-based medical therapy (EBM) and overall mortality in high-risk patients with critical limb-threatening ischaemia (CLTI), compared with patients with myocardial infarction (MI).

Methods and results

Using Danish registries, we identified patients 40–100 years of age with a first-time hospitalization for CLTI or MI from 2008–2018 and grouped them into CLTI, MI, and CLTI and history of MI (CLTI + MI). We examined the likelihood of filling prescriptions with EBM [i.e. antiplatelets (Aps), lipid-lowering agents (LLAs), angiotensin-converting enzyme inhibitor (ACEi), or angiotensin II-receptor blockers (ARBs)] within 3 months after discharge among survivors. Further, we assessed the adjusted 3-year mortality rates. We included 92 845 patients: 14 941 with CLTI (54.7% male), 74 830 with MI (64.6% male) and 3,074 with CLTI + MI (65.2% male). Patients with CLTI and CLTI + MI were older and had more comorbidities than patients with MI. Compared with patients with MI, the unadjusted odds ratios of filling prescriptions were 0.15 [confidence interval (CI): 0.14–0.15] for AP, 0.26 (CI: 0.25–0.27) for LLA, and 0.71 (CI: 0.69–0.74) for ARB/ACEi in patients with CLTI, and 0.22 (CI: 0.20–0.24) for AP, 0.38 (CI: 0.35–0.42) for LLA, and 1.17 (CI: 1.08–1.27) for ARB/ACEi in patients with CLTI + MI. Adjusted analyses showed similar results. Compared with patients with MI, adjusted 3-year hazard ratios for mortality were 1.69 (CI: 1.64–1.74) in patients with CLTI and 1.60 (CI: 1.51–1.69) in patients with CLTI + MI.

Conclusion

Patients with CLTI were undertreated with EBM and carried a more adverse prognosis, as compared with patients with MI, despite similar guidelines.
GoatFADS2controlling fatty acid metabolism is directly regulated bySREBP1in mammary epithelial cells
Authors: Wu Jiao , Luo Jun , Xia Yingying , An Xuetong , Guo Peng , He Qiuya , Tian Huibin , Hu Qingyong , Li Cong , Wang Hui
Published: January 2023

Goat milk provides benefits to human health due to its richness in bioactive components, such as polyunsaturated fatty acids (PUFAs). The fatty acid desaturase 2 (FADS2) is the first rate-limiting enzyme in PUFAs biosynthesis. However, its role and transcriptional regulation mechanisms in fatty acid metabolism in dairy goat remain unclear. Here, our study revealed that the FADS2 gene was highly expressed during the peak lactation compared with the dry period, early lactation, and late lactation. The content of triacylglycerol (TAG) was enhanced with the increasing mRNA expression of TAG synthesis genes (diacylglycerol acyltransferase 1/2, DGAT1/2) in FADS2-overexpressed goat mammary epithelial cells (GMECs). Overexpression of FADS2 was positively correlated with the elevated concentrations of dihomo-gamma-linolenic acid (DGLA) and docosahexaenoic acid (DHA) in GMECs. BODIPY staining showed that FADS2 promoted lipid droplet accumulation in GMECs. To clarify the transcriptional regulatory mechanisms of FADS2, 2,226 bp length of FADS2 promoter was obtained. Deletion mutation assays revealed that the core region of FADS2 promoter was located between the −375 and −26 region, which contained SRE1 (−361/−351) and SRE2 (−191/−181) cis-acting elements of transcription factor sterol regulatory element-binding protein 1 (SREBP1). Overexpression of SREBP1 enhanced relative luciferase activity of the single mutant of SRE1 or SRE2, vice versa, and failed to alter the relative luciferase activity of the joint mutant of SRE1 and SRE2. Chromatin immunoprecipitation (ChIP) and site-directed mutation assays further demonstrated that SREBP1 regulated the transcription of the FADS2 gene by binding to SRE sites in vivo and in vitro. In addition, the mRNA levels of FADS2 were significantly decreased by targeting SRE1 and SRE2 sites in the genome via the CRISPR interference (CRISPRi) system. These findings establish a direct role for FADS2 regulating TAG and fatty acid synthesis by SREBP1 transcriptional regulation in dairy goat, providing new insights into fatty acid metabolism in mammary gland of ruminants.
Breast Imaging Fellowship Consortium: Developing a Comprehensive Virtual Educational Platform for Breast Imaging Fellows
Authors: Wahab Rifat A , Patel Mitva , McLaughlin Carol , Kulkarni Kirti , Nair Bronwyn , Mullen Lisa , Vijapura Charmi
Published: January 2023

Creating a comprehensive didactic curriculum for breast imaging fellows can be a demanding undertaking, especially considering that most breast practices are understaffed because of the COVID-19 pandemic and amid rising clinical volumes. This leaves little time for didactic education. In this article, we present our approach to creating a collaborative weekly multidisciplinary didactic lecture series involving multiple institutions, using the Society of Breast Imaging’s suggested fellowship curriculum as the foundation. We discuss the advantages for both trainees and faculty, including fostering camaraderie, networking, and engagement among breast imaging fellows. Faculty have the opportunity for professional development by leveraging their clinical expertise through selecting didactic topics in their niche. This creates a pathway for speaking faculty to be recognized as regional and national experts.