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© 2014 Macmillan Publishers Limited.Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRNAs) are crucial regulators of cardiovascular pathology and represent intrigu

Abstract Introduction There is a lack of clear indications to carrying out an Akin osteotomy in addition to scarf osteotomy. Recent studies have shown that a proximal distal phalangeal articular angle (PDPAA) of > 8° as an indication to carrying out additional Akin osteotomy correlates with better radiological outcomes with lesser risk of recurrence. Our study aimed to validate carrying out the additional Akin osteotomy at a PDPAA > 8° while looking into functional outcomes which have not been studied. Methods Patients who underwent scarf and combined scarf and Akin osteotomy in our institutional registry was identified. Patient reported outcome measures were compared between patients who underwent scarf and combined scarf and Akin osteotomy. The Visual Analogue Scale (VAS), American Orthopedic Foot and Ankle Score (AOFAS), Short Form-36 Physical Component Score (PCS) and Mental Component Score (MCS) were measured pre-operatively and across a follow up period of 2 years. Results A total of 212 cases were identified. At a PDPAA > 8, there was no difference in VAS, AOFAS, PCS and MCS between patients that had isolated scarf osteotomy and those that received combined scarf and Akin osteotomy pre-operatively, and at 6 months. However, at 2 years post-operatively, patients that received scarf and Akin osteotomy had a significantly better AOFAS score as compared to patients with isolated scarf osteotomy (82.3 ± 15.3 vs 88.4 ± 13.0, p = 0.0224). On the contrary, at a PDPAA 8° can serve as a valid indication to carrying out additional Akin on top of scarf osteotomy based on functional outcomes. However, further studies should investigate a PDPAA threshold that is lower than 8°, which can potentially allow more patients to receive the additional Akin osteotomy that can bring better functional outcomes.

Summary: Patients who suffer hip fractures become immobile with reduced quality of life. Our study aims to assess which cemented or cementless hemiarthroplasty resulted in better mobility or quality-of-life scores. Our retrospective review showed that both have similar scores after matching for age, gender, body mass index and comorbidities. Introduction: Hip fractures have mortality rates of up to 10% at 1 month and 30% at 1 year, as well as significant morbidity. This paper seeks to compare mobility and quality-of-life scores of cemented against uncemented hemiarthroplasty for the displaced neck of femur fractures. Our hypothesis is that there is no difference between the mobility and quality of life of patients treated with cemented or uncemented bipolar hemiarthroplasty. Methods: A retrospective review of registry data on hemiarthroplasties performed in our institution between 2011 and 2019 was conducted. From this dataset, 70 cemented hemiarthroplasties and 238 uncemented hemiarthroplasties were identified. Patients were assessed pre- and post-operatively, at 6 weeks, 3 months, 6 months and 12 months to determine functional recovery through mobility and quality-of-life scores. Results: On propensity score matching, both groups showed a reduction in Parker mobility score from 6.5 to 4 ( p = 0.91), SF-36 physical function scores from 52.5 (cemented) to 30 and 57.5 (uncemented) to 25 ( p = 0.79). Comparing the delta changes from pre-fall after matching, no significant differences were observed. From the analysis of the matched set of data, treatment of neck of femur using cemented or non-cemented bipolar hip prosthesis resulted in similar mobility and quality-of-life scores. Conclusion: In our analysis, there was no statistically significant difference in the mobility or quality-of-life scores of the patients undergoing cemented versus uncemented hemiarthroplasty for the displaced neck of femur fractures.

Roslina Abdul Manap,1 Li Cher Loh,2 Tengku Saifudin Tengku Ismail,3 Abdul Razak Muttalif,4 George Kutty Simon,5 Rosalind Beng Hong Toh,6 Mohd Razali Norhaya,7 Noor Aliza Md Tarekh,8 Che Wan Aminuddin Hashim,9 Mohammad Fauzi Abdul Rani,10 Aziah Ahmad Mahayiddin111Department of Medicine, UniversitiKebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia; 2Department of Medicine, Penang Medical College, Penang, Malaysia; 3Department of Medicine, Faculty of Medicine UniversitiInstitutTeknologi MARA, Selangor, Malaysia; 4Department of Respiratory Medicine, Penang Hospital, Penang, Malaysia; 5Department of Respiratory Medicine, Hospital SultanahBahiyah, Alor Star, Kedah, Malaysia; 6Hospital Ipoh, Ipoh, Malaysia; 7Hospital SultanahNurZahirah, Kuala Terengganu, Malaysia; 8Hospital SultanahAminah, Johor Bahru, Malaysia; 9Hospital UniversitiSains Malaysia, Kelantan, Malaysia; 10Hospital TengkuAmpuanAfzan, Kuantan, Malaysia; 11Institute of Respiratory Medicine, Kuala Lumpur, MalaysiaBackground: Budesonide/formoterol used for both maintenance and reliever therapy has been shown to benefit patients with persistent asthma. We evaluated patient satisfaction and asthma control among Malaysian patients prescribed budesonide/formoterol as single maintenance and reliever therapy in a real-life clinical practice.Methods: Adult patients diagnosed with partially controlled or uncontrolled asthma were recruited in a 6-month, prospective, open-label study involving ten hospital-based chest clinics in Malaysia. Patients were prescribed one or two inhalations of budesonide/formoterol Turbuhaler (160/4.5 µg per inhalation) twice daily as maintenance therapy and additional inhalation as reliever therapy. Maintenance doses were decided by physicians based on Global Initiative for Asthma-defined treatment objectives. The primary outcome measure was the change in mean Satisfaction with Asthma Treatment Questionnaire (SATQ) scores from baseline to an average of 3 months and 6 months. Secondary outcome was the change in mean Asthma Control Questionnaire 5-item version (ACQ-5) scores from baseline to an average of 3 months and 6 months and the proportion of patients achieving the minimum clinically important difference.Results: Of 201 eligible patients recruited, 195 completed the study. Overall, SATQ mean (standard deviation) score was significantly improved from 5.1 (0.76) at baseline to 5.5 (0.58) (P < 0.001). The increase was observed in all domains of SATQ and had occurred at 3 months for most patients. ACQ-5 mean (standard deviation) score was significantly reduced from 2.2 (1.13) at baseline to 1.2 (0.95) (P < 0.001). A total of 132 (67.7.1%) patients had achieved the minimal clinically important difference (≥0.5) of ACQ-5 scores at study end.Conclusion: In a nationwide study, budesonide/formoterol maintenance and reliever therapy achieved greater patient satisfaction and better asthma control compared with previous conventional asthma regimes among Malaysian patients treated in a real-life practice setting. Such an approach may represent an important treatment alternative for our local patients with persistent asthma.Keywords: asthma, asthma control, Malaysia, maintenance and reliever therapy, satisfaction, Symbicort, budesonide/formoterol

Background: ATP citrate lyase (ACLY) is a key enzyme in de novo lipogenesis that generates acetyl-CoA from citrate. Although fatty acids are required for energy production and biomass synthesis in the heart, the regulatory mechanisms of ACLY-mediated de novo lipogenesis in pathological cardiac fibroblasts remain unknown. The aim of this study was to investigate the biological role of ACLY in cardiac remodeling., Methods: Adeno-associated virus serotype 9-mediated shRNA targeting Acly was intravenously injected into C57BL/6J male mice. The mice were subsequently continuously infused with a mixture of angiotensin II and phenylephrine. Cardiac phenotypes were evaluated via histological staining. Cell proliferation assays, stable isotope tracing with 13C-labeled glucose, and chromatin immunoprecipitation assays were performed using human cardiac fibroblasts., Results: ACLY expression was upregulated in the heart sections of mice treated with angiotensin II/phenylephrine, in particular in fibrotic areas. Masson trichrome staining revealed that Acly gene silencing significantly reduced cardiac fibrosis in these mice. Both siRNA-mediated ACLY knockdown and pharmacological ACLY inhibition suppressed the proliferation and expression of fibrous proteins in cultured human cardiac fibroblasts stimulated with transforming growth factor-β. Mechanistically, ACLY inhibition reduced de novo lipogenesis, limiting the fatty acid supply essential for cellular growth and proliferation. It also decreased H3K9 and H3K27 acetylation, in addition to the presence of acetylated H3K9 and H3K27 at the promoter regions of fibrotic genes., Conclusions: Our findings demonstrate that ACLY plays an important role in maladaptive cardiac fibrosis. ACLY could be a novel therapeutic target to prevent the development of heart failure.

Background: With the aging of the population, the number of patients with chronic heart failure (CHF) and comorbidities is increasing in Japan. Among the comorbidities, cardiorenal anemia syndrome (CRAS) is particularly important, but the age-specific prevalence and prognosis of CRAS remain unclear., Methods and Results: The KUNIUMI registry chronic cohort is a prospective observational study of CHF (Stages B-D) in Awaji Island. In this study, we analyzed 1,646 patients registered in the KUNIUMI registry and categorized them into 4 groups: Group 1 included patients without cardiac failure (Stage B); Group 2 consisted of patients with cardiac failure but without renal failure or anemia; Group 3 comprised patients with both cardiac failure and renal failure but without anemia; and Group 4 (CRAS) included patients with cardiac failure, renal failure, and anemia. The primary endpoint was composite of all-cause-death and heart failure hospitalization. The proportion of patients with CRAS increased with age. Furthermore, Group 4 showed a significantly worse prognosis than other groups (log-rank P<0.01). On Cox proportional hazard regression analysis, compared with patients without cardiac failure, renal failure, or anemia, the age- and sex-adjusted hazard ratio for the primary endpoint in those with CRAS was 8.94 (95% confidence interval: 5.36-14.92)., Conclusions: The prevalence of CRAS in CHF increases with age, and the prognosis associated with CRAS is generally worse compared with other comorbidities.

Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. This study aims to identify the monocyte-macrophage heterogeneity and interactions of these cells with non-immune cells, and to identify functional biomarkers in patients with AF. Therefore, we assess the single cell landscape of left atria (LA), using a combination of single cell and nucleus RNA-seq. Myeloid cells in LA tissue are categorized into five macrophage clusters, three monocyte clusters, and others. Cell-Chat analysis revealed that monocytes and IL1B + macrophages send epidermal growth factor (EGF) signals to fibroblasts. Amphiregulin (AREG) is the most upregulated gene in monocytes and IL1B + macrophages in the AF group, compared with healthy controls from other groups. Serum AREG levels are higher in patients with persistent AF. These data suggested that EGF signaling pathway could be a therapeutic target for AF and serum AREG levels provide an effective biomarker for predicting persistent AF., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Stage B heart failure (HF) refers to structural heart disease without signs or symptoms of HF, so that early intervention may delay or prevent the onset of overt HF. However, stage B HF is a very broad concept, and risk stratification of such patients can be challenging., Methods and Results: We conducted a prospective study of data for 1646 consecutive patients with HF from the KUNIUMI (Kobe University Heart Failure Registry in Awaji Medical Center) registry chronic cohort. The definition of HF stages was based on current guidelines for classification of 29 patients as stage A HF, 761 as stage B HF, 827 as stage C HF, and 29 patients as stage D HF. The primary end point was the time-to-first-event defined as cardiovascular death or HF hospitalization within 2.0 years of follow-up. A maximum of 6 adjustment factor points was assigned based on Cox proportional hazards analysis findings for the hazard ratio (HR) of independent risk factors for the primary end point: 1 point for anemia, estimated glomerular filtration rate <45 mL/min per 1.73 m 2 , brain natriuretic peptide ≥150 pg/mL, and average ratio of early transmitral flow velocity to early diastolic mitral annular velocity >14, and 2 points for clinical frailty scale >3. Patients with stage B HF were stratified into 3 groups, low risk (0-1 points), moderate risk (2-3 points), and high risk (4-6 points). Based on this scoring system (BEEAF 2 [brain natriuretic peptide, estimated glomerular filtration rate, ratio of early transmitral flow velocity to early diastolic mitral annular velocity, anemia, and frailty]), the outcome was found to become worse in accordance with risk level. High-risk patients with stage B HF and patients with stage C HF showed similar outcomes., Conclusions: Our scoring system offers an easy-to-use evaluation of risk stratification for patients with stage B HF.

The pathophysiology of variant transthyretin (TTR) amyloidosis (ATTRv) is associated with destabilizing mutations in the TTR tetramer. However, why TTR with a wild-type genetic sequence misfolds and aggregates in wild-type transthyretin amyloidosis (ATTRwt) is unknown. Here, we evaluate kinetic TTR stability with a newly developed ELISA system in combination with urea-induced protein denaturation. Compared with that in control patients, endogenous TTR in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) exhibited thermodynamic instability, indicating that circulating TTR instability may be associated with the pathogenesis of ATTRwt as well as ATTRv. Our findings provide new insight into the underlying mechanisms of ATTRwt., (© 2024. The Author(s).)

The 88 th Annual Scientific Meeting of the Japanese Circulation Society (JCS2024) was held from Friday, March 8 th to Sunday, March 10 th in Kobe, Japan. The main theme of this 3-day meeting was "The Future of Cardiology: Challenges in Overcoming Cardiovascular Disease". As COVID-19 has been finally conquered, with revision of its categorization under the Infectious Disease Control Law and relaxation of infection prevention measures, it was once again possible to have face-to-face presentations and lively discussion. JCS2024 was a major success, with 19,209 participants and attendees, thanks to the greatly appreciated cooperation and support from all affiliates.

Background: Although low high-density lipoprotein cholesterol (HDL-C) levels are a common metabolic abnormality associated with insulin resistance, their role in cardiovascular risk stratification remains controversial. Recently, we developed a simple, high-throughput, cell-free assay system to evaluate the "cholesterol uptake capacity (CUC)" as a novel concept for HDL functionality. In this study, we assessed the CUC in patients with hypertriglyceridemia and diabetes mellitus., Methods: The CUC was measured using cryopreserved serum samples from 285 patients who underwent coronary angiography or percutaneous coronary intervention between December 2014 and May 2019 at Kobe University Hospital., Results: The CUC was significantly lower in diabetic patients (n = 125) than in nondiabetic patients (93.0 vs 100.7 arbitrary units (A.U.), P = 0.002). Patients with serum triglyceride (TG) levels >150 mg/dL (n = 94) also had a significantly lower CUC (91.8 vs 100.0 A.U., P = 0.004). Furthermore, the CUC showed a significant inverse correlation with TG, hemoglobin A1c (Hb A1c), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Finally, the HDL-C/Apolipoprotein A1 (ApoA1) ratio, calculated as a surrogate index of HDL particle size, was significantly positively correlated with the CUC (r2 = 0.49, P < 0.001), but inversely correlated with TG levels (r2 = -0.30, P < 0.001)., Conclusions: The CUC decreased in patients with hypertriglyceridemia and diabetes mellitus, and HDL particle size was a factor defining the CUC and inversely correlated with TG levels, suggesting that impaired CUC in insulin-resistant states was partially due to the shift in HDL towards smaller particles. These findings provide a better understanding of the mechanisms underlying impaired HDL functionality., (Published by Oxford University Press on behalf of Association for Diagnostics & Laboratory Medicine 2024.)

Gut microbiome dysbiosis contributes to the pathophysiology of both gestational diabetes mellitus (GDM) and its associated adverse outcomes in the woman and offspring. Even though GDM prevalence, complications, and outcomes vary among different ethnic groups, limited information is available about the influence of ethnicity on gut microbiome dysbiosis in pregnancies complicated by GDM. This pilot prospective cohort study examined the impact of ethnicity on gut dysbiosis in GDM among three Asian ethnic groups (Chinese, Malay, Indian) living in Singapore, and investigated the potential modulatory roles of diet and lifestyle modifications on gut microbiome post-GDM diagnosis. Women with GDM (n = 53) and without GDM (n = 16) were recruited. Fecal samples were collected at 24-28- and 36-40-weeks' gestation and analyzed by targeted 16S rRNA gene-based amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) analysis was performed to evaluate differences between groups. Differentially abundant taxa were identified by DeSeq2 based analysis. Functional prediction was performed using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2). Among women with GDM, gut microbiome from different ethnicities harbored common microbial features. However, among those without GDM, there was contrasting microbiome composition between ethnic groups. Microbial members such as Collinsella, Blautia, Ruminococcus, Ruminococcus gnavus, Ruminococcus torques, and Eubacterium hallii groups were differentially enriched (p < 0.05) in women with GDM compared to those without. Among women with GDM, no differences in alpha- and beta- diversity were observed when comparing 24-28 weeks' samples with 36-40 weeks' samples, a period covering intense dietary and lifestyle modification, suggesting an inability to modulate gut microbiota through classic GDM management. Women with GDM have a distinct gut microbiome profile which harbours common features across different Asian ethnic groups, consistent with the notion that specific microbes are involved in the pathogenesis of insulin resistance, pro-inflammatory conditions, and other metabolic dysregulation known to be present in GDM., (© 2024. The Author(s).)

Background: Early detection and intervention for preclinical heart failure (HF) are crucial for restraining the potential increase in patients with HF. Thus, we designed and conducted a single-center retrospective cohort study to confirm the efficacy of B-type natriuretic peptide (BNP) for the early detection of preclinical HF in a primary care setting., Methods and results: We investigated 477 patients with no prior diagnosis of HF who were under the care of general practitioners. These patients were categorized into 4 groups based on BNP concentrations: Category 1, 0 pg/mL≤BNP≤35 pg/mL; Category 2, 35 pg/mL200 pg/mL. There was a marked and statistically significant increase in the prevalence of preclinical HF with increasing BNP categories: 19.9%, 57.9%, 87.5%, and 96.0% in Categories 1, 2, 3, and 4, respectively. Compared with Category 1, the odds ratio of preclinical HF in Categories 2, 3, and 4 was determined to be 5.56 (95% confidence interval [CI] 3.57-8.67), 23.70 (95% CI 8.91-63.11), and 171.77 (95% CI 10.31-2,861.93), respectively., Conclusions: Measuring BNP is a valuable tool for the early detection of preclinical HF in primary care settings. Proactive testing in patients at high risk of HF could play a crucial role in addressing the impending HF pandemic.

This study examines the global air travel demand pattern using complex network analysis. Using the data for the top 50 airports based on passenger volume rankings, we investigate the relationship between network measures of nodes (airports) in the global flight network and their passenger volume. The analysis explores the network measures at various spatial scales, from individual airports to metropolitan areas and countries. Different attributes, such as flight route length and the number of airlines, are considered in the analysis. Certain attributes are found to be more relevant than others, and specific network measure models are found to better capture the dynamics of global air travel demand than others. Among the models, PageRank is found to be the most correlated with total passenger volume. Moreover, distance-based measures perform worse than the ones emphasising the number of airlines, particularly those counting the number of airlines operating a route, including codeshare. Using the PageRank score weighted by the number of airlines, we find that airports in Asian cities tend to have more traffic than expected, while European and North American airports have the potential to attract more passenger volume given their connectivity pattern. Additionally, we combine the network measures with socio-economic variables such as population and GDP to show that the network measures could greatly augment the traditional approaches to modelling and predicting air travel demand. We'll also briefly discuss the implications of the findings in this study for airport planning and airline industry strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huynh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Stress has garnered significant attention as a prominent risk factor for inflammation-related diseases, particularly cardiovascular diseases (CVDs). However, the precise mechanisms underlying stress-driven CVDs remain elusive, thereby impeding the development of preventive and therapeutic strategies. To explore the correlation between plasma lipid metabolites and human depressive states, liquid chromatography-mass spectrometry (LC/MS) based analysis of plasma and the self-rating depression (SDS) scale questionnaire were employed. We also used a mouse model with restraint stress to study its effects on plasma lipid metabolites and stenotic vascular remodeling following carotid ligation. In vitro functional and mechanistic studies were performed using macrophages, endothelial cells, and neutrophil cells. We revealed a significant association between depressive state and reduced plasma levels of 4-oxoDHA, a specific omega-3 fatty acid metabolite biosynthesized by 5-lipoxygenase (LO), mainly in neutrophils. In mice, restraint stress decreased plasma 4-oxoDHA levels and exacerbated stenotic vascular remodeling, ameliorated by 4-oxoDHA supplementation. 4-oxoDHA enhanced Nrf2-HO-1 pathways, exerting anti-inflammatory effects on endothelial cells and macrophages. One of the stress hormones, noradrenaline, reduced 4-oxoDHA and the degraded 5-LO in neutrophils through the proteasome system, facilitated by dopamine D2-like receptor activation. Our study proposed circulating 4-oxoDHA levels as a stress biomarker and supplementation of 4-oxoDHA as a novel therapeutic approach for controlling stress-related vascular inflammation., (© 2024. The Author(s).)

Background: Diabetes increases the risk of heart failure (HF). 3-Hydroxyisobutyric acid (3-HIB) is a muscle-derived metabolite reflecting systemic insulin resistance. In this study, we investigated the prognostic impact of 3-HIB in patients with chronic HF., Methods and results: The KUNIUMI Registry chronic cohort is a community-based cohort study of chronic HF in Awaji Island, Japan. We analyzed the association between serum 3-HIB concentrations and adverse cardiovascular (CV) events in 784 patients from this cohort. Serum 3-HIB concentrations were significantly higher in patients with than without diabetes (P=0.0229) and were positively correlated with several metabolic parameters. According to Kaplan-Meier analysis, rates of CV death and HF hospitalization at 2 years were significantly higher among HF patients without diabetes in the high 3-HIB group (3-HIB concentrations above the median; i.e., >11.30 μmol/L) than in the low 3-HIB group (log-rank P=0.0151 and P=0.0344, respectively). Multivariable Cox proportional hazard models adjusted for established risk factors for HF revealed high 3-HIB as an independent predictor of CV death (hazard ratio [HR] 1.82; 95% confidence interval [CI] 1.16-2.85; P=0.009) and HF hospitalization (HR 1.72; 95% CI 1.17-2.53, P=0.006) in HF patients without diabetes, whereas no such trend was seen in subjects with diabetes., Conclusions: In a community cohort, circulating 3-HIB concentrations were associated with prognosis in chronic HF patients without diabetes.

Elevated circulating homocysteine (Hcy) is a well-known risk factor for cardiovascular diseases (CVDs), including coronary artery disease (CAD) and heart failure (HF). It remains unclear how Hcy and its derivatives relate to left ventricular (LV) diastolic function. The aim of the present study was to investigate the relationship between plasma Hcy-related metabolites and diastolic dysfunction (DD) in patients with heart disease (HD). A total of 62 HD patients with preserved LV ejection fraction (LVEF ≥ 50%) were enrolled. Plasma Hcy and its derivatives were measured by liquid chromatography‒mass spectrometry (LC-MS/MS). Spearman's correlation test and multiple linear regression models were used to analyze the associations between metabolite levels and LV diastolic function. The cystine/methionine (CySS/Met) ratio was positively correlated with LV diastolic function, which was defined from the ratio of mitral inflow E and mitral e' annular velocities (E/e') (Spearman's r = 0.43, p < 0.001). When the subjects were categorized into two groups by E/e', the high-E/e' group had a significantly higher CySS/Met ratio than the low-E/e' group (p = 0.002). Multiple linear regression models revealed that the CySS/Met ratio was independently associated with E/e' after adjustment for age, sex, body mass index (BMI), diabetes mellitus, hypertension, chronic kidney disease (CKD),　hemoglobin, and lipid peroxide (LPO) {standardized β (95% CI); 0.14 (0.04-0.23); p = 0.005}. Hcy, CySS, and Met did not show a significant association with E/e' in the same models. A high plasma CySS/Met ratio reflected DD in patients with HD., (© 2023. Springer Nature Japan KK, part of Springer Nature.)