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Bile acids (BA) are synthesized in the human liver and undergo metabolism by host gut bacteria. In diseased states, gut microbial dysbiosis may lead to high primary unconjugated BA concentrations and significant perturbations to secondary BA. Hence, it is important to understand the microbial-mediated formation kinetics of secondary bile acids using physiologically relevant ex vivo human faecal microbiota models. Here, we optimized an ex vivo human faecal microbiota model to recapitulate the metabolic kinetics of primary unconjugated BA and applied it to investigate the formation kinetics of novel secondary BA metabolites and their sequential pathways. We demonstrated (1) first-order depletion of primary BA, cholic acid (CA) and chenodeoxycholic acid (CDCA), under non-saturable conditions and (2) saturable Michaelis-Menten kinetics for secondary BA metabolite formation with increasing substrate concentration. Notably, relatively lower Michaelis constants (K m) were associated with the formation of deoxycholic acid (DCA, 14.3 μM) and lithocholic acid (LCA, 140 μM) versus 3-oxo CA (>1000 μM), 7-keto DCA (443 μM) and 7-keto LCA (>1000 μM), thereby recapitulating clinically observed saturation of 7α-dehydroxylation relative to oxidation of primary BA. Congruently, metagenomics revealed higher relative abundance of functional genes related to the oxidation pathway as compared to the 7α-dehydroxylation pathway. In addition, we demonstrated gut microbial-mediated hyocholic acid (HCA) and hyodeoxycholic acid (HDCA) formation from CDCA. In conclusion, we optimized a physiologically relevant ex vivo human faecal microbiota model to investigate gut microbial-mediated metabolism of primary BA and present a novel gut microbial-catalysed two-step pathway from CDCA to HCA and, subsequently, HDCA. [Display omitted] • Ex vivo human faecal model for primary bile acid (BA) metabolism was optimized. • Concentration-dependent formation kinetics of secondary BA were recapitulated. • Novel gut microbial metabolism of chenodeoxycholic acid to 6α-hydroxylated BA. [ABSTRACT FROM AUTHOR]

Urban watersheds from point sources are potential reservoirs of antibiotic resistance genes (ARGs). However, few studies have investigated urban watersheds of non-point sources. To understand the type of ARGs and bacteria that might carry such genes, we investigated two non-point source urban watersheds with different land-use profiles. Antibiotic resistance levels of two watersheds (R1, R3) were examined using heterotrophic plate counts (HPC) as a culturing method to obtain counts of bacteria resistant to seven antibiotics belonging to different classes (erythromycin, kanamycin, lincomycin, norfloxacin, sulfanilamide, tetracycline and trimethoprim). From the HPC study, 239 antibiotic resistant bacteria were characterized for resistance to more antibiotics. Furthermore, ARGs and antimicrobial biosynthesis genes were identified using GeoChip version 5.0 to elucidate the resistomes of surface waters in watersheds R1 and R3. The HPC study showed that water samples from R1 had significantly higher counts of bacteria resistant to erythromycin, kanamycin, norfloxacin, sulfanilamide, tetracycline and trimethoprim than those from R3 (Analysis of Similarity (ANOSIM), R = 0.557, p < 0.01). Of the seven antibiotics tested, lincomycin and trimethoprim resistant bacteria are greater in abundances. The 239 antibiotic resistant isolates represent a subset of resistant bacterial populations, including bacteria not previously known for resistance. Majority of the isolates had resistance to ampicillin, vancomycin, lincomycin and trimethoprim. GeoChip revealed similar ARGs in both watersheds, but with significantly higher intensities for tetX and β-lactamase B genes in R1 than R3. The genes with the highest average normalized intensities in R1 and R3 were tetracycline (tet) and fosfomycin ( fosA) resistance genes, respectively. The higher abundance of tetX genes in R1 is congruent with the higher abundance of tetracycline resistant HPC observed in R1 samples. Strong correlations ( r ≥ 0.8) of efflux pumps with antimicrobial biosynthesis genes suggest that natural production of antimicrobials may act as a selective pressure of transporter proteins in the absence of antibiotics from anthropogenic sources. In conclusion, distinct antibiotic resistant bacteria phylotypes and a variety of ARGs were present in the non-point sources urban watersheds of different land-use profiles, suggesting that ARG risk assessments and monitoring studies need to include these types of watersheds. [ABSTRACT FROM AUTHOR]

Microbial community compositions were determined for three soil horizons and drain sediments within an anthropogenically disturbed coastal acid sulfate landscape using 16S rRNA gene tagged 454 pyrosequencing. Diversity analyses were problematic due to the high microbiological heterogeneity between each geochemical replicate. Taxonomic analyses combined with measurements of metal(loid) bioaccessibility identified significant correlations to genera (5% phylogenetic distance) abundances. A number of positive correlations between genera abundance and bioaccessible metals concentrations were observed, indicating that metal(loid) tolerance influences microbial community compositions in these types of landscapes. Of note, Mn was highly bioaccessible (⩽24% total soil Mn); and Mn bioaccessibility positively correlated to Acidobacterium abundance, but negatively correlated to Holophaga abundance. Two unidentified archaeal genera belonging to Crenarchaeota were also correlated to bio-accessible Mn concentrations, suggesting these genera can exploit Mn redox chemistry. [ABSTRACT FROM AUTHOR]

Background—Most methods for assessing microvascular function are not readily available in the cardiac catheterization laboratory. The aim of this study is to determine whether the Index of Microcirculatory Resistance (IMR), measured at the time of primary percutaneous coronary intervention, is predictive of death and rehospitalization for heart failure. Methods and Results—IMR was measured immediately after primary percutaneous coronary intervention in 253 patients from 3 institutions with the use of a pressure-temperature sensor wire. The primary end point was the rate of death or rehospitalization for heart failure. The prognostic value of IMR was compared with coronary flow reserve, TIMI myocardial perfusion grade, and clinical variables. The mean IMR was 40.3±32.5. Patients with an IMR >40 had a higher rate of the primary end point at 1 year than patients with an IMR <40 (17.1% versus 6.6%; P=0.027). During a median follow-up period of 2.8 years, 13.8% experienced the primary end point and 4.3% died. An IMR >40 was associated with an increased risk of death or rehospitalization for heart failure (hazard ratio [HR], 2.1; P=0.034) and of death alone (HR, 3.95; P=0.028). On multivariable analysis, independent predictors of death or rehospitalization for heart failure included IMR >40 (HR, 2.2; P=0.026), fractional flow reserve 5S0.8 (HR, 3.24; P=0.008), and diabetes mellitus (HR, 4.4; f<0.001). An IMR >40 was the only independent predictor of death alone (HR, 4.3; P=0.02). Conclusions—An elevated IMR at the time of primary percutaneous coronary intervention predicts poor long-term outcomes. [ABSTRACT FROM AUTHOR]

Treatment of displaced femoral neck fractures with total hip replacement (THR) in appropriately selected patients has become more widely accepted. The use of the posterior approach for THR remains controversial due to concerns regarding dislocation, the cause of which is multi-factorial. This study is a single surgeon series of 45 consecutive active, healthy patients (mean age 78 years) with displaced femoral neck fractures treated with THR through a posterior approach. Large diameter heads (32mm in 47%, ≥36mm in 48% of patients) and an anatomic posterior soft tissue repair were utilised to minimize the risk of dislocation. Outcomes were reported at a mean of 2 and 6 years. The mortality rate was 13% at 2 years and 40% at 6 years. All revision surgery (4.4%) was performed for dislocations which occurred in 6.7% of patients. Good VAS pain, OHS and SF-12 scores were reported both at 2 and 6 years. Patient satisfaction with the results of surgery was high. [ABSTRACT FROM AUTHOR]

Summary Chloroform (CF, CHCl3) is a recalcitrant and toxic environmental pollutant. In this communication we report for the first time a microbial community capable of complete CF dechlorination by metabolic processes. Cultures derived from subsurface soil (3.5 m) could sustain complete dechlorination of CF at levels of least 360 µM at a rate of 40 µM per day. Scrutiny of CF dechlorination revealed two metabolic processes at work. First, CF was respired to dichloromethane (DCM, CH2Cl2), which was then fermented to acetate, hydrogen and carbon dioxide. Elevated hydrogen partial pressures were found to inhibit the fermentation process. Interspecies hydrogen transfer was observed in the form of methanogenesis and acetogenesis. This suggests that the dechlorination process required syntrophic partners to maintain low hydrogen partial pressures. 13C-labelled DCM was employed to help elucidate the chemistry of the process and identify bacterial community members involved. CF respiring cultures, where emulsified vegetable oil was supplied as the electron donor and DCM fermenting cultures, where DCM was supplied as the sole organic carbon source were studied separately. Pyrosequencing of these cultures revealed Dehalobacter lineages as a predominant community member in both. Subsequent growth experiments confirmed that the proliferation of Dehalobacter was linked directly to both the dehalorespiration and dehalofermentation processes. [ABSTRACT FROM AUTHOR]

The endothelial progenitor cell (EPC)-capture stent promotes endothelialization and preliminary studies have suggested its safety and feasibility in ST-elevation myocardial infarction (STEMI). Detailed late clinical follow-up and angiographic analyses are, however, limited. We sought to determine late angiographic and clinical outcomes of the Genous EPC-capture stent in primary angioplasty. EPC-capture stents were implanted during primary angioplasty in 489 consecutive patients presenting with STEMI from 2004 through 2008. The first 100 consenting patients undergoing successful stent implantation scheduled to undergo relook coronary angiography at 6 to 12 months were enrolled. Ninety-five patients with 96 lesions were analyzed independently. Mean duration of follow-up coronary angiography was 245 days. In-stent late luminal loss measured 0.87 ± 0.67 mm. Binary restenosis (defined as >50% diameter stenosis) was 28%, with diffuse in-stent restenosis (Mehran class II) as the predominant pattern. Of 27 patients with binary restenosis, 14 (52%) were symptomatic, with 10 patients undergoing target lesion revascularization. Asymptomatic patients had significantly larger reference vessel and in-stent minimal luminal diameters (2.77 ± 0.39 vs 2.54 ± 0.44 mm, p = 0.040; 2.74 ± 0.34 vs 2.31 ± 0.72 mm, p = 0.004, respectively). Follow-up late loss and diameter stenoses were also in favor of the asymptomatic group. Major adverse cardiac event rate was 16% at a mean follow-up of 34 months. There were no cases of Academic Research Consortium–defined stent thrombosis. In conclusion, implantation of the EPC-capture stent during primary angioplasty is associated with a favorable late clinical outcome but with higher than anticipated angiographic late loss. [ABSTRACT FROM AUTHOR]

Environments contaminated with mixtures of chlorinated hydrocarbons represent a formidable challenge for bioremediation because biodegradation of all components of the mixture must be demonstrated. In this study a soil site contaminated with hexachloro-1,3-butadiene (HCBD), hexachlorobenzene (HCB), and perchloroethene (PCE) was investigated. Environmental parameters (including toxicity) and microbial community composition were characterized. The lack of scientific literature on HCBD biodegradation led to attempts to develop HCBD-respiring enrichment cultures and to test the hypothesis that known PCE-degrading cultures could dechlorinate HCBD. No HCBD dechlorination was observed. An alternative approach, using electron shuttles to degrade the mixture of chlorinated hydrocarbons, was compared with the activity of zero-valent iron. The authors conclude that electron shuttles offer promise for the in situ treatment of mixtures of chlorinated hydrocarbons. [ABSTRACT FROM AUTHOR]

An inflammatory cause of atrial fibrillation (AF) has been proposed on the basis of the presence of lymphocytic infiltrates in the biopsy results of patients with lone AF, alterations of C-reactive protein (CRP) and interleukin-6 levels in subjects with AF, and the time course of postoperative AF. Many previous studies exploring inflammatory factors in AF have been confounded by concomitant medical illnesses. Subjects with lone AF provide a unique opportunity to eliminate the effects of associated conditions. We therefore sought to determine CRP levels in homogenous cohorts of patients with lone AF or AF and hypertension. One hundred twenty-one subjects with lone AF, 52 subjects with AF and hypertension, and 75 control subjects were enrolled and studied. Plasma CRP levels were determined using a commercially available immunoassay. There was no significant difference in CRP levels between subjects with lone AF and controls (1.34 vs 1.21 mg/L, p = 0.18). CRP levels in subjects with AF and hypertension were elevated compared with those of controls and those of subjects with lone AF, although this difference was attributable to increased body mass indexes. CRP levels were not elevated in subjects with lone AF compared with controls. In conclusion, these findings clarify previous observations of elevations in CRP levels in subjects with AF and suggest that this marker of systemic inflammation is associated not with the arrhythmia per se, but rather with underlying cardiovascular disease. [Copyright &y& Elsevier]

Objective: To evaluate the safety and efficacy of the X-SIZER thrombectomy device versus the use of abciximab during primary angioplasty for acute ST-elevation myocardial infarction (STEMI). Design: Retrospective analysis of patients undergoing primary angioplasty for STEMI from October 2000 to December 2002 using the X-SIZER thrombectomy device versus abciximab. Setting: National University Hospital, Singapore. Patients: Out of 79 patients, 44 underwent X-SIZER use, while 35 received adjunct abciximab. Both groups were similarly represented with regards to age, gender, risk factors, target vessel site/diameter, cardiogenic shock, and onset of chest pain to procedure time. The infarct-related artery was occluded in 88.6% in both groups. Interventions: A 2-mm X-SIZER was used in 34/44 (77.3%), while a 1.5-mm device was used in the remainder. Final TIMI 3 flow was obtained in 38/44 (86.4%) in the X-SIZER group compared to 26/35 (74.3%) in the abciximab group (P = 0.175). Main Outcome Measures: Coronary TIMI flow rate, electrocardiogram (ECG) resolution, slow flow/no reflow phenomenon, and patient outcome (death, cardiac failure, or repeat revascularization) at 1 month. Results: ECG resolution and slow flow/no reflow were better in the X-SIZER group (77.3% vs 54.3%, P = 0.031; 9.1% vs 25.7%, P = 0.047, respectively). Patient outcome at 1 month was, however, not significantly different (18.2% vs 17.1%, P = 0.904, respectively, for X-SIZER and abciximab). Conclusion: X-SIZER thrombectomy during primary percutaneous coronary intervention for thrombus-laden STEMI is a safe and effective strategy. When compared to patients receiving abciximab, it was associated with improved ECG resolution, less slow flow/no reflow and a trend to better TIMI 3 flow. (J Interven Cardiol 2005;18:267–273) [ABSTRACT FROM AUTHOR]

Objectives: We sought to characterize natriuretic peptide levels in a cohort of rigorously characterized subjects with lone atrial fibrillation (AF). Background: Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are sensitive biomarkers of cardiac contractile dysfunction. Both peptides have been reported to be elevated in cohorts with AF, but previous studies have included subjects with underlying structural heart disease. We studied these hormones in 150 subjects with lone AF. Methods: Study subjects had electrocardiographic evidence of at least one episode of AF and a structurally normal heart on echocardiography. Subjects were excluded if they had a history of a myocardial infarction, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or hypertension that preceded the onset of AF. Control subjects were obtained from a healthy outpatient primary care population. Plasma pro-ANP and N-terminal pro-BNP (nt-pro-BNP) levels were determined using commercially available immunoassays. Results: A total of 150 serial subjects with lone AF were enrolled and studied, the majority during normal sinus rhythm. Median levels of nt-pro-BNP were significantly elevated in subjects with lone AF as compared with control subjects (166 vs. 133 fmol/ml, p = 0.0003). There was no significant difference in pro-ANP levels between subjects with lone AF and control subjects (1,730 vs. 1,625 fmol/ml, p = 0.90). Conclusions: Discordant natriuretic peptide levels were observed in this homogeneous population of subjects with lone AF. This biomarker pattern, which is present even in sinus rhythm, may represent an underlying subclinical predisposition to this common arrhythmia. [Copyright &y& Elsevier]

Background: Vascular disease is a feature of aging, and coronary vascular events are a major source of morbidity and mortality in rare premature aging syndromes. One such syndrome is caused by mutations in the lamin A/C (LMNA) gene, which also has been implicated in familial insulin resistance. A second gene related to premature aging in man and in murine models is the KLOTHO gene, a hypomorphic variant of which (KL-VS) is significantly more common in the first-degree relatives of patients with premature coronary artery disease (CAD). We evaluated whether common variants at the LMNA or KLOTHO genes are associated with rigorously defined premature CAD. Methods: We identified 295 patients presenting with premature acute coronary syndromes confirmed by angiography. A control group of 145 patients with no evidence of CAD was recruited from outpatient referral clinics. Comprehensive haplotyping of the entire LMNA gene, including the promoter and untranslated regions, was performed using a combination of TaqMan® probes and direct sequencing of 14 haplotype-tagging single nucleotide polymorphisms (SNPs). The KL-VS variant of the KLOTHO gene was typed using restriction digest of a PCR amplicon. Results: Two SNPs that were not in Hardy Weinberg equilibrium were excluded from analysis. We observed no significant differences in allele, genotype or haplotype frequencies at the LMNA or KLOTHO loci between the two groups. In addition, there was no evidence of excess homozygosity at the LMNA locus. Conclusion: Our data do not support the hypothesis that premature CAD is associated with common variants in the progeroid syndrome genes LMNA and KLOTHO. [ABSTRACT FROM AUTHOR]

The association of coronary artery spasm and myocardial bridging is very uncommon and may represent a distinct clinical entity. Three patients are described, presenting with acute coronary syndrome associated with myocardial bridging and coronary artery spasm. The relationship and respective roles of myocardial bridging and spasm, however, remain uncertain and may be consequent to a direct effect on endothelial function from the compressive effect of myocardial bridging. The role of intracoronary nitroglycerin in these patients is unresolved. [ABSTRACT FROM AUTHOR]

In this paper, we describe a case-study exploring the use of 600 MW of power from New Zealand's Manapouri Power Station to produce hydrogen for export via water electrolysis. Three H 2 carriers were considered: liquid H 2 , ammonia, and toluene hydrogenation/methylcyclohexane dehydrogenation. Processes were simulated in Aspen's HYSYS for each of the carriers to determine their associated energy and annualised capital expenditure costs. We found that the total capital investment for all carriers was surprisingly consistent, but with quite different splits between the electrolysis and carrier formation plants. Based on our analysis the energy availability for liquid H 2 ranged from 53.9 to 60.7% depending on the energy cost associated with cryogenic H 2 liquefaction. The energy availability for liquid ammonia was 37.5% after conversion back to H 2 , or 53.6% if the ammonia can be used directly as a fuel. For toluene/methylcyclohexane the energy availability was 41.2%. The total of the electricity and annualised capital costs per kg of H 2 ranged from NZ$5.63 to NZ$6.43 for liquid H 2 , NZ$6.24 to NZ$8.91 for ammonia and was NZ$7.86 for toluene/methylcyclohexane, using a net electricity cost of NZ$70/MWh. The cost of hydrogen (or energy in the case of direct use ammonia) was more strongly influenced by the efficiency of energy retention than on capital investment, as the electricity costs contributed approximately two thirds of total costs. In the long-term, liquid hydrogen looks to be the most versatile H 2 carrier, but significant infrastructure investment is required. • Capital costs of large-scale hydrogen carrier formation plants estimated. • Liquid hydrogen, ammonia and methylcyclohexane carrier systems compared. • Combined cost of electrolysis and carrier formation plants similar: from NZ$1.85 to $2.04 billion for a power envelope of 600 MW. • Energy efficiency of carrier system determines final cost of hydrogen energy. • Efficiency of ammonia comparable to liquid hydrogen, but only for direct use. [ABSTRACT FROM AUTHOR]

Aim: Patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. Methods: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan‐Meier curve was constructed for long‐term all‐cause mortality. Cox regression analysis was used to investigate independent predictors of long‐term all‐cause mortality. Results: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow‐up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all‐cause mortality (6.8% vs. 3.6%, p <.001) at 30 days, with unfavourable mortality rates sustained in the long‐term (18.3% vs. 14.5%, p =.001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long‐term all‐cause mortality (hazard ratio 1.330, 95% confidence interval 1.106‐1.598, p =.002). Conclusion: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long‐term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI. [ABSTRACT FROM AUTHOR]

Dietary changes are known to alter the composition of the gut microbiome. However, it is less understood how repeatable and reversible these changes are and how diet switches affect the microbiota in the various segments of the gastrointestinal tract. Here, a treatment group of conventionally raised laboratory mice is subjected to two periods of western diet (WD) interrupted by a period of standard diet (SD) of the same duration. Beta-diversity analyses show that diet-induced microbiota changes are largely reversible (q = 0.1501; PERMANOVA, weighted-UniFrac comparison of the treatment-SD group to the control-SD group) and repeatable (q = 0.032; PERMANOVA, weighted-UniFrac comparison of both WD treatments). Furthermore, we report that diet switches alter the gut microbiota composition along the length of the intestinal tract in a segment-specific manner, leading to gut segment-specific Firmicutes/Bacteroidota ratios. We identified prevalent and distinct Amplicon Sequencing Variants (ASVs), particularly in genera of the recently described Muribaculaceae, along the gut as well as ASVs that are differentially abundant between segments of treatment and control groups. Overall, this study provides insights into the reversibility of diet-induced microbiota changes and highlights the importance of expanding sampling efforts beyond the collections of fecal samples to characterize diet-dependent and segment-specific microbiome differences. [ABSTRACT FROM AUTHOR]

Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017–2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28–7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18–4.96), lower arterial pH (aOR 0.02, CI 0.00–0.31), higher lactate (aOR 2.42, CI 1.00–1.19), and lower hemoglobin (aOR 0.83, CI 0.71–0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS. [ABSTRACT FROM AUTHOR]

Physician visual assessment (PVA) in invasive coronary angiography (ICA) is the current clinical method to determine stenosis severity and guide percutaneous coronary intervention. This study sought to evaluate the effect of sex differences in assessing coronary stenosis severity between PVA and quantitative coronary angiography (QCA). 209 patients with coronary artery disease (288 coronary lesions) underwent ICA and fractional flow reserve (FFR). ICA image processing including PVA and QCA was used to quantify diameter stenosis (DS). The difference of DS (ΔDS) between PVA and QCA was defined as DS PVA -DS QCA. DS ≥50% was considered anatomically obstructive. FFR ≤0.8 was defined as myocardial ischemia. Mean ± SD age was 63 ± 9 years. There were no significant differences in DS PVA (61.1 ± 16.3% vs 60.1 ± 18.9%) and DS QCA (53.1 ± 12.1% vs 55.4 ± 14.3%) between females and males. However, ΔDS between PVA and QCA was higher in females (8.0 ± 10.9%) than in males (4.7 ± 10.9%) (P = 0.03). Thirty-four of 72 vessels (47.2%) in female patients and 75 of 216 vessels (34.7%) in male patients were classified differently by at least one grade using PVA compared to QCA assessment. DS PVA and DS QCA were negatively correlated with FFR in females (r PVA = −0.397, r QCA = −0.448) with an even stronger negative correlation in males (r PVA = −0.607, r QCA = −0.607). ROC analysis demonstrated that DS QCA had better discrimination capability for myocardial ischemia (FFR ≤ 0.80) than DS PVA in both sexes (P < 0.05). A systematic bias was found in PVA (QCA reference) for overestimating severity of coronary artery disease in females compared to males. • We compared physician visual assessment (PVA) and quantitative coronary angiography (QCA) in both sexes to assess stenosis. • The association of PVA and QCA with invasive fractional flow reserve (FFR) was investigated in both sexes. • PVA tended to overestimate the assessment of diameter stenosis, with greater overestimation in females than in males. • Accuracy of PVA and QCA in the diagnosis of myocardial ischemia (FFR < 0.8) was inferior in female patients. • QCA and FFR should be integrated into clinical practice to ensure more precise assessment of coronary stenosis in females. [ABSTRACT FROM AUTHOR]

A Desulfitobacterium sp. strain AusDCA of the Peptococcaceae family capable of respiring 1,2-dichloroethane (1,2-DCA) to ethene anaerobically with ethanol or hydrogen as electron donor at pH 5.0 with optimal range between pH 6.5–7.5 was isolated from an acidic aquifer near Sydney, Australia. Strain AusDCA is distant (94% nucleotide identity) from its nearest phylogenetic neighbor, D. metallireducens, and could represent a new species. Reference gene-based quantification of growth indicated a doubling time of 2 days in cultures buffered at pH 7.2, and a yield of 7.66 (± 4.0) × 106 cells µmol−1 of 1,2-DCA. A putative 1,2-DCA reductive dehalogenase was translated from a dcaAB locus and had high amino acid identity (97.3% for DcaA and 100% for DcaB) to RdhA1B1 of the 1,2-DCA respiring Dehalobacter strain WL. Proteomic analysis confirmed DcaA expression in the pure culture. Dehalogenation of 1,2-DCA (1.6 mM) was observed in batch cultures established from groundwater at pH 5.5 collected 38 days after in situ bioaugmentation but not in cultures established with groundwater collected at the same time from wells not receiving bioaugmentation. Overall, strain AusDCA can tolerate lower pH than previously characterized organohalide respiring bacteria and remained viable in groundwater at pH 5.5. [ABSTRACT FROM AUTHOR]

Rotator cuff tears (RCTs) are a common cause of shoulder pain and weakness in the elderly (age > 65yrs) and result in reduced quality of life, loss of income and a burden on health care. With the elderly population living longer there is a growing interest in the effective and efficient management of RCTs. In a majority of cases, the initial treatment is conservative, with physical therapy, analgesics and possibly corticosteroid or plasma rich protein injections. There are various surgical options, including rotator cuff repair, superior capsule reconstruction, subacromial decompression and reverse shoulder arthroplasty. The aim of this article is to provide a narrative review of evidence guiding the management options for RCTs in the elderly. [ABSTRACT FROM AUTHOR]

Genomes of two trichloroethene (TCE)-respiring Dehalococcoides (Dhc) mccartyi, strains MB and 11a, were sequenced to identify reductive dehalogenases (RDase) responsible for oraganohalide respiration. Transcription analyses were conducted to verify the roles of RDase subunit A genes (rdhA) in chloroethene respiration. Some interesting features of the strain MB draft genome include a large genome size, two CRISPR-cas type I systems, and 38 rdhA genes. Strain 11a has a stream-lined genome with 11 rdhA genes, of which nine are distinct. Quantitative real-time PCR transcription analysis of RDase gene transcripts showed that a single RDase gene, designated mbrA, was up-regulated upon exposure to TCE and no other RDase genes were considerably expressed in strain MB. A single RDase gene, designated vcrA, was up-regulated upon exposure to TCE and expressed at a steady level until all chloroethenes were completely dechlorinated to ethene at 147 h in strain 11a. Overall, this study reports the genomes of two distinct Dhc strains; both contain numerous uncharacterized RDase genes, but in each strain only one such gene was expressed highly during organohalide respiration. [ABSTRACT FROM AUTHOR]

Presents a case study of a man with a history of Kawasaki disease. Impact of myocradial infarction on Kawasaki disease; Importance of thrombosuction to the treatment of stenosis; Symptoms of Kawasaki disease such as polymorphous rash; Impact of intravenous gamma globulin on the risk of a coronary aneurysm.

Abstract: Distal protection using FilterWire EX has been shown to be effective in reducing the incidence of debris embolization and no-reflow phenomenon in saphenous vein graft (SVG) intervention. We present a case of mechanical obstruction of antegrade flow by atherothrombotic debris collected in the FilterWire EX after stent implantation of the ostial SVG lesion, masqueraded as no-reflow phenomenon. The condition was promptly reverted by thrombosuction using an Export Aspiration Catheter. A heavy debris burden was recovered by the thrombosuction and there was no evidence of myonecrosis after the procedure. We emphasize that different distal protection device can complement each other in special situations. A brief overview of the various approaches in preventing distal embolization in SVG intervention was also given. [Copyright &y& Elsevier]

Osteoarthritis of the shoulder is caused by progressive cartilage wear of the glenohumeral joint. Its prevalence is increasing due to our ageing population and it may affect up to one-third of people over 60 years of age. Patients usually complain of pain with restricted shoulder movement and function. Initial treatment should be non-operative, such as activity modification, oral analgesics (e.g. non-steroidal anti-inflammatories) and possibly physical therapy or corticosteroid injections. Patients with ongoing severe pain and functional restriction despite non-operative treatment would be candidates for surgery, usually a shoulder replacement. There are various forms of shoulder replacements and the aim of this review is to discuss the types available, the indications for using one over another and recent worldwide trends in the use of shoulder replacements. [ABSTRACT FROM AUTHOR]

Aim: To examine the prevalence and prognosis of hepatic steatosis and fibrosis in post‐acute myocardial infarction (AMI) patients. Methods: Patients presenting with AMI to a tertiary hospital were examined from 2014 to 2021. Hepatic steatosis and advanced hepatic fibrosis were determined using the Hepatic Steatosis Index and fibrosis‐4 index, respectively. The primary outcome was all‐cause mortality. Cox regression models identified determinants of mortality after adjustments and Kaplan–Meier curves were constructed for all‐cause mortality, stratified by hepatic steatosis and advanced fibrosis. Results: Of 5765 patients included, 24.8% had hepatic steatosis, of whom 41.7% were diagnosed with advanced fibrosis. The median follow‐up duration was 2.7 years. Patients with hepatic steatosis tended to be younger, female, with elevated body mass index and an increased metabolic burden of diabetes, hypertension and hyperlipidaemia. Patients with hepatic steatosis (24.6% vs. 20.9% mortality, P <.001) and advanced fibrosis (45.6% vs. 32.9% mortality, P <.001) had higher all‐cause mortality rates compared with their respective counterparts. Hepatic steatosis (adjusted hazard ratio 1.364, 95% CI 1.145‐1.625, P =.001) was associated with all‐cause mortality after adjustment for confounders. Survival curves showed excess mortality in patients with hepatic steatosis compared with those without (P =.002). Conclusions: Hepatic steatosis and advanced fibrosis have a substantial prevalence among patients with AMI. Both are associated with mortality, with an incrementally higher risk when advanced fibrosis ensues. Hepatic steatosis and fibrosis could help risk stratification of AMI patients beyond conventional risk factors. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphism rs6903956 has been identified as one of the genetic risk factors for coronary artery disease (CAD). However, rs6903956 lies in a non-coding locus on chromosome 6p24.1. We aim to interrogate the molecular basis of 6p24.1 containing rs6903956 risk alleles in endothelial disease biology. We generated induced pluripotent stem cells (iPSCs) from CAD patients (AA risk genotype at rs6903956) and non-CAD subjects (GG non-risk genotype at rs6903956). CRISPR-Cas9-based deletions (Δ63-89bp) on 6p24.1, including both rs6903956 and a short tandem repeat variant rs140361069 in linkage disequilibrium, were performed to generate isogenic iPSC-derived endothelial cells. Edited CAD endothelial cells, with removal of 'A' risk alleles, exhibited a global transcriptional downregulation of pathways relating to abnormal vascular physiology and activated endothelial processes. A CXC chemokine ligand on chromosome 10q11.21, CXCL12 , was uncovered as a potential effector gene in CAD endothelial cells. Underlying this effect was the preferential inter-chromosomal interaction of 6p24.1 risk locus to a weak promoter of CXCL12 , confirmed by chromatin conformation capture assays on our iPSC-derived endothelial cells. Functionally, risk genotypes AA/AG at rs6903956 were associated significantly with elevated levels of circulating damaged endothelial cells in CAD patients. Circulating endothelial cells isolated from patients with risk genotypes AA/AG were also found to have 10 folds higher CXCL12 transcript copies/cell than those with non-risk genotype GG. Our study reveals the trans -acting impact of 6p24.1 with another CAD locus on 10q11.21 and is associated with intensified endothelial injury. [Display omitted] • 6p24.1 locus containing rs6903956 is related to endothelial activation pathways. • Chromosomes 6p24.1 and 10q11.21 are spatially organized in endothelial cells. • 6p24.1 is in close genomic proximity to a weak promoter of CXCL12 that resides on 10q11.21 • Risk allele 'A' of rs6903956 is associated with endothelial injury in CAD patients. [ABSTRACT FROM AUTHOR]

Background: Real-world data on long-term (> 5 years) weight loss and obesity-related complications after newer bariatric surgical procedures are currently limited. The aim of this longitudinal study was to examine the effectiveness and sustainability of bariatric surgery in a cohort with clinically severe obesity in a multidisciplinary publicly funded service in two teaching hospitals in New South Wales, Australia. Methods: Patients were adults with complex clinically severe obesity with a BMI ≥ 35 kg/m2 and at least three significant obesity-related comorbidities, who underwent bariatric surgeries between 2009 and 2017. Detailed obesity-related health outcomes were reported from annual clinical data and assessments for up to 9 years of follow-up. Data were also linked with the national joint replacement registry. Results: A total of 65 eligible patients were included (mean, 7; range, 3–12 significant obesity-related comorbidities); 53.8% female; age 54.2 ± 11.2 years, with baseline BMI 52.2 ± 12.5 kg/m2 and weight 149.2 ± 45.5 kg. Most underwent laparoscopic sleeve gastrectomy (80.0%), followed by laparoscopic adjustable gastric banding (10.8%) and one anastomosis gastric bypass (9.2%). Substantial weight loss was maintained over 9 years of follow-up (p < 0.001 versus baseline). Significant total weight loss (%TWL ± SE) was observed (13.2 ± 2.3%) following an initial 1-year preoperative intensive lifestyle intervention, and ranged from 26.5 ± 2.3% to 33.0 ± 2.0% between 1 and 8 years following surgery. Type 2 diabetes mellitus (T2DM), osteoarthritis-related joint pain and depression/severe anxiety were the most common metabolic, mechanical and mental health comorbidities, with a baseline prevalence of 81.5%, 75.4% and 55.4%, respectively. Clinically significant composite cumulative rates of remission and improvement occurred in T2DM (50.0–82.0%) and hypertension (73.7–82.9%) across 6 years. Dependence on continuous positive airway pressure treatment in patients with sleep-disordered breathing fell significantly from 63.1% to 41.2% in 6 years. Conclusion: Bariatric surgery using an intensive multidisciplinary approach led to significant long-term weight loss and improvement in obesity-related comorbidities among the population with clinically complex obesity. These findings have important implications in clinical care for the management of the highest severity of obesity and its medical consequences. Major challenges associated with successful outcomes of bariatric surgery in highly complex patients include improving mental health in the long run and reducing postoperative opioid use. Long-term follow-up with a higher volume of patients is needed in publicly funded bariatric surgery services to better monitor patient outcomes, enhance clinical data comparison between services, and improve multidisciplinary care delivery. [ABSTRACT FROM AUTHOR]

Background: The clinical significance of coronary artery ectasia (CAE) is not yet fully understood. We aimed to examine differences in clinical and procedural characteristics, clinical management, and outcomes in patients with CAE undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI).Methods: This was a retrospective analysis of consecutive patients presenting with STEMI with a culprit native coronary artery from July 2015 to June 2019. Patients were divided into CAE and Non-CAE groups as detected on coronary angiography during PPCI. Comparison between groups was made for baseline clinical and procedural characteristics, as well as complications, pharmacological treatment, and follow-up outcomes.Results: 36/1780 (2.0%) patients were found to have CAE. Patients with CAE had a median age of 57.1 ± 11.7 years and were more likely to be male 33/36 (91.7%). Diabetes was less commonly seen in the CAE group (11.1% vs 31.4%, p = 0.010), and there were no differences in the proportion of patients with hypertension and hyperlipidemia. Patients with CAE had more involvement of right coronary artery (RCA) culprit vessel (63.9% vs. 38.4%, p = 0.026), less coronary stenting (25.0% vs 87.2%, p < 0.001) and post-PPCI TIMI 3 flow (69.4% vs 95.5%, P < 0.001), and were more likely to be discharged with oral anticoagulants (36.1% vs 7.6%, p < 0.001). At 3-year follow-up, all-cause mortality rates were higher in the non-CAE group (0.0% vs 11.5%, p < 0.028), suggesting that CAE was not associated with unfavorable long-term outcome. On multivariate analysis, CAE was not an independent predictor of MACE.Conclusion: Despite lower rates of post-PPCI TIMI 3 flow, CAE was not associated with unfavorable long-term outcome. [ABSTRACT FROM AUTHOR]

The role of Lp(a) in multi-ethnic Asian populations with coronary artery disease (CAD) has not been well established. The aims of this study were (i) to investigate whether Lp(a) is a predictor of CAD, and (ii) amongst patients with CAD, to ascertain whether Lp(a) is a predictor of acute myocardial infarction (AMI) and severity of CAD. We compared three cardiovascular phenotypes from patients recruited at coronary angiography. CAD was defined as ≥50% coronary artery stenosis and subdivided into a group with AMI history (CAD+AMI+) and a group without (CAD+AMI-). Minimal CAD group (CAD-) was defined as normal or <30% coronary artery stenosis and no AMI. The severity of CAD was defined using the modified Gensini score. We studied 2025 patients comprising 94.5% men and 61.4% of Chinese ethnicity. The median Lp(a) level was highest in CAD+AMI+, followed by CAD+AMI- and CAD- (26.2, 20.1, and 15.8 nmol/L respectively). Similarly, the frequency of patients with Lp(a) ≥120 nmol/L were in the same order (11.8%, 9.1% and 2.4%). Lp(a) levels were highest among Asian Indians, followed by Malays and Chinese patients (p < 0.001). Lp(a) levels and Lp(a) ≥120 nmol/L were significant predictors of CAD (Odds ratio (OR) = 1.12 per 10 nmol/L increment, p < 0.001, and OR = 5.41 p = 0.004 respectively). Among patients with CAD, higher Lp(a) levels were associated with increased AMI risk (OR = 1.02 per 10 nmol/L increment, p = 0.024). Lp(a) ≥120 nmol/L was positively associated with CAD severity (p = 0.020). Plasma Lp(a) concentration is a positive predictor of CAD and AMI in a mostly male South East Asian population. [Display omitted] • Higher Lp(a) levels were associated with increased coronary artery disease (CAD) risk in multi-ethnic Asians. • Lp(a) was associated with increased acute myocardial infarction (AMI) risk and severity of CAD. • Distribution of Lp(a) is a right skew pattern in Chinese, Malays and Asians Indians. [ABSTRACT FROM AUTHOR]

Wastewater treatment plants (WWTPs) are major collection pools of antibiotics of which low concentrations may induce antibiotic resistance in their microbial communities and pose threat to human health. However, information is still limited on the microbial community alteration in WWTPs upon exposure to low-dose antibiotics due to absence of negative control systems without input of resistant bacteria and resistance genes. Here we report the impact of trace erythromycin (ERY) and dehydrated erythromycin (ERY-HO) on microbial community dynamics in three long-term (1 year) running sequencing batch reactors (SBRs), R1 (ERY-HO), R2 (ERY), and negative control R3. The PhyloChip microarray analysis showed that ERY-HO and ERY significantly altered their microbial communities based on bacterial richness (e.g., 825 operational taxonomic units (OTUs) in R1, 699 OTUs in R2, and 920 OTUs in R3) and population abundance (15 and 48 subfamilies with >80 % abundance decrease in R1 and R2, respectively). ERY-HO and ERY have broad but distinct antimicrobial spectrums. For example, bacteria of all the major phyla (i.e., Proteobacteria, Actinobacteria, Bacteroidetes, and Chloroflexi) present in SBRs were severely inhibited by ERY-HO and ERY, but bacteria of Acidobacteria, Chlorobi, Firmicutes, Nitrospira and OP10 phyla were only inhibited by ERY. Very limited bacterial groups showed antibiotic resistance to ERY-HO or ERY through forming biofilms (e.g., Zoogloea) or synthesizing resistant proteins (e.g., Thauera, Candidatus Accumulibacter, Candidatus Competibacter, and Dechloromonas) in the SBRs. Inhibition was observed to be the main effect of ERY-HO and ERY on microbial communities in the reactors. The results would broaden our knowledge of effects of low-dose antibiotics on microbial communities in WWTPs. [ABSTRACT FROM AUTHOR]

Background: Biodegradable polymer drug eluting stents (BP-DES) may offer the advantage of vascular healing in ST-segment elevation myocardial infarction (STEMI). Long-term outcome data comparing BP-DES and second-generation durable polymer drug eluting stents (DP-DES) in STEMI is lacking. This study aims to compare the long-term clinical outcomes of BP-DES versus second-generation DP-DES in STEMI.Methods: This is an observational study of consecutive patients with STEMI who received either BP-DES (n = 854) or DP-DES (n = 708) during primary percutaneous coronary intervention (PCI) from 1st February 2007 to 31st December 2016. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (MI), and target lesion revascularization with follow up till 30th November 2019.Results: The baseline demographics, lesion and procedural characteristic were similar between the two groups except for more prior MI and chronic obstructive pulmonary disease in the BP-DES group. At a median follow up of 4.2 years (interquartile range: 2.6-6.2 years), the incidence of TLF was similar between BP-DES and DP-DES (adjusted hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70-1.26). Likewise, incidence of major adverse cardiovascular events (MACE: all-cause death, any MI or target vessel revascularization) and definite stent thrombosis were similar in both groups (MACE: adjusted HR 1.04, 95% CI 0.82-1.32; definite stent thrombosis: adjusted HR 1.06, 95% CI 0.31-3.64).Conclusion: Among patients with STEMI who underwent primary PCI, BP-DES and DP-DES implantation was associated with similar long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

A reactive iron barrier in a contaminated aquifer with low pH was found to dechlorinate 1,2-dichloroethane (1,2-DCA) in situ. This chlorinated ethane is known to resist abiotic reduction by zero valent iron. Samples taken up-gradient and within the barrier were used to inoculate anaerobic batch cultures amended with various electron donors. Cultures inoculated with groundwater from within the reactive iron barrier reduced 1,2-DCA to ethene. The same effect could be achieved by simultaneously supplying hydrogen while neutralising pH. The presence of iron or hydrogen at neutral pH had negligible effects on 1,2-DCA reduction in cultures inoculated with groundwater sampled up-gradient of the barrier. Molecular microbial community characterisation revealed that Dehalobacter species were more abundant in groundwater sampled from within the barrier. These findings suggest reactive iron barriers represent a remediation technology for 1,2-DCA degradation acting through in situ recruitment of 1,2-DCA reducing bacteria such as Dehalobacter. [ABSTRACT FROM AUTHOR]

Background: We sought to report the incidence of angiographic no-reflow and clinical outcomes of elderly patients who have undergone primary percutaneous coronary intervention at a tertiary institution in Singapore over a period of 10 years. Methods: A total of 141 patients (60% male) aged 75 or above underwent primary PCI between 1998 and 2007. Their average age was 80±5 years. Cardiogenic shock complicating STEMI on presentation accounted for 15% of the patients. Results: At baseline, 103 (73%) patients have impaired TIMI flow grade (TIMI 0–2), and 38 (27%) have normal flow (TIMI 3). At the end of the procedure, 44 (31.2%) patients had no-reflow phenomenon (TIMI 0–2), whereas 97 (68.8%) achieved normal antegrade flow. Post-procedure corrected TIMI frame count was analyzable in 66% ( n=93) of the patients. Post-procedure corrected TIMI frame count was>28 in 37.6% ( n=35) of patients. In-hospital, 30-day and six-month mortalities were 20.6, 25.5% and 27.7%, respectively. Multivariable analysis showed that age 80 or above, low systolic blood pressure and final TIMI 0–2 flow independently predicted six-month mortality. Conclusions: We found that one-third of the treated patients developed no-reflow phenomenon. Six-month mortality was 27.7%, most were cardiac deaths that occurred during index hospitalization. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular magnetic resonance (CMR) sequences are commonly used to obtain a complete description of the function and structure of the heart, provided that accurate measurements are extracted from images. New methods of extraction of information are being developed, among them, deep neural networks are powerful tools that showed the ability to perform fast and accurate segmentation. Iq1n order to reduce the time spent by reading physicians to process data and minimize intra- and inter-observer variability, we propose a fully automatic multi-scan CMR image analysis pipeline. Methods: Sequence specific U-Net 2D models were trained to perform the segmentation of the left ventricle (LV), right ventricle (RV) and aorta in cine short-axis, late gadolinium enhancement (LGE), native T1 map, post-contrast T1, native T2 map and aortic flow sequences depending on the need. The models were trained and tested on a set of data manually segmented by experts using semi-automatic and manual tools. A set of parameters were computed from the resulting segmentations such as the left ventricular and right ventricular ejection fraction (EF), LGE scar percentage, the mean T1, T1 post, T2 values within the myocardium, and aortic flow. The Dice similarity coefficient, Hausdorff distance, mean surface distance, and Pearson correlation coefficient R were used to assess and compare the results of the U-Net based pipeline with intra-observer variability. Additionally, the pipeline was validated on two clinical studies. Results: The sequence specific U-Net 2D models trained achieved fast (≤ 0.2 s/image on GPU) and precise segmentation over all the targeted region of interest with high Dice scores (= 0.91 for LV, = 0.92 for RV, = 0.93 for Aorta in average) comparable to intra-observer Dice scores (= 0.86 for LV, = 0.87 for RV, = 0.95 for aorta flow in average). The automatically and manually computed parameters were highly correlated (R = 0.91 in average) showing results superior to the intra-observer variability (R = 0.85 in average) for every sequence presented here. Conclusion: The proposed pipeline allows for fast and robust analysis of large CMR studies while guaranteeing reproducibility, hence potentially improving patient's diagnosis as well as clinical studies outcome. [ABSTRACT FROM AUTHOR]

Background: Haptoglobin (Hp) is a plasma protein with strong anti‐inflammation and antioxidant activities. Its plasma level is known to be inversely associated with many inflammatory diseases, including cardiovascular diseases. However, the association of HP genetic variants with coronary artery disease (CAD) severity/mortality, and how they interact with common CAD risk factors are largely unknown. Methods: We conducted the analysis in a Singaporean Chinese CAD population with Gensini severity scores (N = 582) and subsequently evaluated the significant findings in an independent cohort with cardiovascular mortality (excluding stroke) as outcome (917 cases and 19,093 controls). CAD risk factors were ascertained from questionnaires, and stenosis information from medical records. Mortality was identified through linkage with the nationwide registry of births and deaths in Singapore. Linear regression analysis between HP genetic variant (rs217181) and disease outcome were performed. Interaction analyses were performed by introducing an interaction term in the same regression models. Results: Although rs217181 was not significantly associated with CAD severity and cardiovascular mortality (excluding stroke) in all subjects, when stratified by hypertension status, hypertensive individuals with the minor T allele have more severe CAD (β = 0.073, SE = 0.030, p = 0.015) and non‐hypertensive individuals with the T allele have lower risk for mortality (odds ratio = 0.771 (0.607–0.980), p = 0.033). Conclusion: HP genetic variant is not associated with CAD severity and mortality in the general population. However, hypertensive individuals with the rs217181 T allele associated with higher Hp levels had more severe CAD while non‐hypertensive individuals with the same allele had lower risk for mortality in the Chinese population. [ABSTRACT FROM AUTHOR]

Few studies have investigated the prevalence of frailty in the Australian general population. This study determined the prevalence of frailty in a population-based sample of older adults and examined the relationship between frailty and comorbid conditions. Men (n = 347) and women (n = 360) aged ≥ 60 year from the Geelong Osteoporosis Study (GOS) were assessed between 2016-2019 and 2011-2014, respectively. Frailty was identified using a modified Fried frailty phenotype. Prevalence estimates were standardised to the 2011 Australian population. Kruskal-Wallis test and χ2 test were used to analyse data. For women, mean standardised prevalence estimates were 18.3% (14.1-22.5) for frail, 54.1% (47.3-60.8) pre-frail and 22.9% (18.9-26.8) robust. Corresponding estimates for men were 13.1% (9.8-16.3) frail, 47.8% (42.0-53.6) pre-frail and 27.3% (22.7-31.8) robust. Women who were frail were older, shorter, tended to have a higher body mass index (BMI) and used more medications compared to other groups. Compared to robust women, those who were frail were more likely to have cardio-metabolic (OR 3.5 (0.7-20.0)), pulmonary (OR 3.5 (1.5-8.4)) and musculoskeletal (OR 10.1 (2.1-48.0)) conditions. Frail men were older, had a higher BMI and were more likely to have musculoskeletal conditions (OR 5.8 (2.8-12.3)) and tended to be from a lower SES. No further associations were observed. This study reported the prevalence of frail and pre-frail individuals in a population-based sample of Australian men and women. Frailty was associated with musculoskeletal conditions for both men and women; however, associations with cardio-metabolic and pulmonary comorbidities were evident in women only. [ABSTRACT FROM AUTHOR]

Background/purpose: Percutaneous coronary intervention (PCI) of diffuse coronary artery disease (CAD) is associated with higher adverse clinical events. This study aimed to compare the clinical outcomes of patients treated with single long 48 mm contemporary drug eluting stents (SL-DES) versus two overlapping contemporary drug eluting stents (OL-DES) for very-long CAD.Methods/materials: We analyzed the clinical outcome of 117 patients with SL-DES and 101 patients with OL-DES who underwent PCI between 1st July 2013 to 31st December 2016. The primary endpoint was target lesion failure (TLF) at two years, defined as a composite of cardiac mortality, target vessel myocardial infarction and target lesion revascularization.Results: Mean age was 60.8 ± 10.5 years for SL-DES group and 60.5 ± 11.9 years in the OL-DES group. SL-DES has longer mean lesion length as compared to OL-DES (43.1 ± 3.7 mm vs. 41.83 ± 2.3 mm p = 0.003). There was no difference in TLF at two years between SL-DES and OL-DES (5.3% vs. 6.4%, adjusted odds ratio 1.43, 95% CI 0.50-4.11). There was one case of probable ST in each group. Contrast volume usage was lower for SL-DES than OL-DES in patients who underwent single vessel PCI.Conclusions: Treatment of very-long CAD showed comparable TLF at two years for SL-DES versus OL-DES. Our results suggest that both strategies are reasonable treatment options for patients with diffuse CAD. [ABSTRACT FROM AUTHOR]

Androgen dependent tissue factor pathway inhibitor regulating protein (ADTRP) is a novel protein associated with coronary artery disease (CAD) susceptibility, and reduced mRNA expression of ADTRP was shown to be associated with increased CAD risk. This study aimed to determine and compare circulating ADTRP levels between CAD patients and controls, and to test the performance of plasma ADTRP as a biomarker for CAD. We measured plasma ADTRP, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high sensitivity-C reactive protein (hs-CRP) levels in 362 CAD patients, 150 angiographically negative CAD controls, and 83 healthy adults with no known clinical or medical conditions using commercial ELISA. Statistical analyses were performed using receiver operator characteristic (ROC) curves, quantile regression and logistic regression, with adjustments for age, gender, ethnicity and BMI. CAD patients had significantly lower plasma ADTRP levels 1,545 (1,087–2,408) pg/ml as compared to CAD controls 2,259 (1,533–3,778) pg/ml and healthy adults 3,904 (2,732–5,463) pg/ml. Plasma ADTRP outperformed the other three inflammatory biomarkers (TNF-α, IL-6 and hs-CRP) for CAD (Area under ROC curve: 0.67, Odds ratio (OR): 0.907). Our study has shown for the first time that ADTRP is present in circulation, and that plasma ADTRP may be a novel independent biomarker for CAD. [ABSTRACT FROM AUTHOR]

Proper inlet boundary conditions are essential for accurate computational fluid dynamics (CFD) modeling. We developed methodology to derive noninvasive FFRB using CFD and computed tomography coronary angiography (CTCA) images. This study aims to assess the influence of brachial mean blood pressure (MBP) and total coronary inflow on FFRB computation. Twenty-two patients underwent both CTCA and FFR measurements. Total coronary flow was computed from left ventricular mass (LVM) measured from CTCA. A total of 286 CFD simulations were run by varying MBP and LVM at 70, 80, 90, 100, 110, 120, and 130% of the measured values. FFRB increased with incrementally higher input values of MBP: 0.78 ± 0.12, 0.80 ± 0.11, 0.82 ± 0.10, 0.84 ± 0.09, 0.85 ± 0.08, 0.86 ± 0.08, and 0.87 ± 0.07, respectively. Conversely, FFRB decreased with incrementally higher inputs value of LVM: 0.86 ± 0.08, 0.85 ± 0.08, 0.84 ± 0.09, 0.84 ± 0.09, 0.83 ± 0.10, 0.83 ± 0.10, and 0.82 ± 0.10, respectively. Noninvasive FFRB calculated using measured MBP and LVM on a total of 30 vessels was 0.84 ± 0.09 and correlated well with invasive FFR (0.83 ± 0.09) (r = 0.92, P < 0.001). Positive association was observed between FFRB and MBP input values (mmHg) and negative association between FFRB and LVM values (g). Respective slopes were 0.0016 and −0.005, respectively, suggesting potential application of FFRB in a clinical setting. Inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. NEW & NOTEWORTHY While brachial mean blood pressure (MBP) and left ventricular mass (LVM) measured from CTCA are the two CFD simulation input parameters, their effects on noninvasive fractional flow reserve (FFRB) have not been systematically investigated. We demonstrate that inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. This is important in the clinical application of noninvasive FFR in coronary artery disease diagnosis. [ABSTRACT FROM AUTHOR]

We evaluated the effects of sleep-study guided multidisciplinary therapy (SGMT) of obstructive sleep apnoea (OSA) in patients presenting with acute coronary syndrome. Eligible patients were randomized into (1) SGMT, comprised a sleep study during the index admission and continuous positive airway pressure and behavioral therapy for those with at least mild OSA or (2) standard therapy. The primary end point was the change in the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level from baseline to the 7-month follow-up. A total of 159 patients completed the trial. Of the 70 patients randomized to SGMT, 21 (30%), 15 (22%) and 27 (39%) were diagnosed with mild, moderate and severe OSA, respectively. Continuous positive airway pressure and a positional pillow were prescribed to 57 (91%) and 6 (9%) patients with OSA. Although plasma NT-proBNP levels were lower after 7 months compared to the baseline, the levels did not differ significantly between the SGMT and standard therapy groups at baseline (579 ± 1117 vs. 611 ± 899 pg/dL, p =.851) or at 7 months (90 ± 167 vs. 93 ± 174 pg/dL, p =.996). The changes in NT-proBNP levels from baseline to 7 months were similar with SGMT and standard therapy (−489 vs. –518 pg/dL, p =.726). Similar findings were observed for the plasma ST2 and hs-CRP levels. OSA screening and multifaceted treatment during the sub-acute phase of acute coronary syndrome did not further reduce the levels of cardiovascular biomarkers when compared with standard therapy. Clinical Trial Registration: clinicaltrial.gov NCT02599298 [ABSTRACT FROM AUTHOR]

Background/purpose: Primary percutaneous coronary intervention (PCI) during acute ST-segment elevation myocardial infarction (STEMI) represents a thrombotic milieu and is associated with delayed healing after stenting. The pro-healing combination sirolimus eluting endothelial progenitor cell (EPC) capture stents encourage early endothelialization after stenting and may be beneficial in the STEMI population. We aim to evaluate the clinical outcomes one year and beyond for patients with STEMI who received the combination sirolimus eluting EPC capture stents during primary PCI.Methods/material: All STEMI patients implanted with combination sirolimus eluting EPC capture stents during primary PCI from November 2013 to December 2016 were enrolled. The primary outcome was target lesion failure (TLF) at in-hospital, one-month, one-year and beyond one year.Results: A total of 260 consecutive STEMI patients (283 lesions) were implanted with 313 combination sirolimus eluting EPC capture stents during primary PCI. Mean age was 56.1 ± 11.2 years and 88.8% were male. One in ten patients (10.9%) had cardiogenic shock on presentation, 7.3% needed mechanical ventilation and 7.7% had intra-aortic balloon pump inserted. A total of 97.9% of lesions achieve final TIMI 3 flow. Device success was seen in all patients. At extended follow up period (median 23.4 months), the clinical outcomes were TLF 8.8%, major adverse cardiovascular events 10.8%, cardiac mortality 4.2%, target vessel myocardial infarction 3.4%, target lesion revascularization 3.8%, and definite stent thrombosis 1.9%.Conclusions: This study demonstrated acceptable clinical outcomes for an all-comers STEMI patients undergoing primary PCI with the use of combination sirolimus eluting EPC cell capture stents. [ABSTRACT FROM AUTHOR]

Purpose: In contemporary total knee arthroplasty (TKA), most often, the goal is to align the femoral component to the epicondylar axis (EA). The posterior condylar axis (PCA) is easier to define than the EA, and thus the relationship of PCA to the EA is then used instead to align the femoral component to the EA. However, the relationship of PCA to EA is not constant and has been reported to differ between varus and valgus knees and with increasing deformity. The aim of this large MRI-based study was to evaluate the relationship between PCA and EA with varying coronal deformity especially with increasing valgus deformity. Methods: EA, PCA, AP (Whiteside's line) and the mechanical axis were obtained from 474 magnetic resonance imaging (MRI) scans used to create patient-specific instrumentation (PSI) for the Biomet Signature (Warsaw, NJ) system. Results: The relationship of EA relative to the PCA showed considerable heterogeneity in both varus and valgus groups. In the valgus group, there was statistically greater external rotation (P < 0.05) of the EA from the PCA with a mean of 2.52° (range − 1.9° to 6°) compared to the varus group with a mean of 2.03° (range − 3.9° to 6.9°). This relationship did not significantly change with increasing severity of coronal malalignment. Externally rotating the femoral cutting guide by 3° from the PCA, 11% (42 of 382) of varus knees would lie outside of ± 3° from EA. In valgus knees, externally rotating the femoral cutting block by 3° or 5° from the PCA, 6.5% (6 of 92) and 33.7% (31 of 92) of knees, respectively, would lie outside of ± 3° from EA. Conclusion: The relationship of PCA to EA is heterogeneous and is not altered significantly with increasing valgus coronal deformity. External rotation beyond 3° from PCA in valgus knees may lead to significant femoral component malrotation in a large proportion cases. [ABSTRACT FROM AUTHOR]