Quantification of Biventricular Strains in Heart Failure With Preserved Ejection Fraction Patient Using Hyperelastic Warping Method

Heart failure (HF) imposes a major global health care burden on society and suffering on the individual. About 50% of HF patients have preserved ejection fraction (HFpEF). More intricate and comprehensive measurement-focused imaging of multiple strain components may aid in the diagnosis and elucidation of this disease. Here, we describe the development of a semi-automated hyperelastic warping method for rapid comprehensive assessment of biventricular circumferential, longitudinal, and radial strains that is physiological meaningful and reproducible. We recruited and performed cardiac magnetic resonance (CMR) imaging on 30 subjects [10 HFpEF, 10 HF with reduced ejection fraction patients (HFrEF) and 10 healthy controls]. In each subject, a three-dimensional heart model including left ventricle (LV), right ventricle (RV), and septum was reconstructed from CMR images. The hyperelastic warping method was used to reference the segmented model with the target images and biventricular circumferential, longitudinal, and radial strain–time curves were obtained. The peak systolic strains are then measured and analyzed in this study. Intra- and inter-observer reproducibility of the biventricular peak systolic strains was excellent with all ICCs > 0.92. LV peak systolic circumferential, longitudinal, and radial strain, respectively, exhibited a progressive decrease in magnitude from healthy control→HFpEF→HFrEF: control (-15.5 ± 1.90, -15.6 ± 2.06, 41.4 ± 12.2%); HFpEF (-9.37 ± 3.23, -11.3 ± 1.76, 22.8 ± 13.1%); HFrEF (-4.75 ± 2.74, -7.55 ± 1.75, 10.8 ± 4.61%). A similar progressive decrease in magnitude was observed for RV peak systolic circumferential, longitudinal and radial strain: control (-9.91 ± 2.25, -14.5 ± 2.63, 26.8 ± 7.16%); HFpEF (-7.38 ± 3.17, -12.0 ± 2.45, 21.5 ± 10.0%); HFrEF (-5.92 ± 3.13, -8.63 ± 2.79, 15.2 ± 6.33%). Furthermore, septum peak systolic circumferential, longitudinal, and radial strain magnitude decreased gradually from healthy control to HFrEF: control (-7.11 ± 1.81, 16.3 ± 3.23, 18.5 ± 8.64%); HFpEF (-6.11 ± 3.98, -13.4 ± 3.02, 12.5 ± 6.38%); HFrEF (-1.42 ± 1.36, -8.99 ± 2.96, 3.35 ± 2.95%). The ROC analysis indicated LV peak systolic circumferential strain to be the most sensitive marker for differentiating HFpEF from healthy controls. Our results suggest that the hyperelastic warping method with the CMR-derived strains may reveal subtle impairment in HF biventricular mechanics, in particular despite a “normal” ventricular ejection fraction in HFpEF

Percutaneous coronary intervention in asians- are there differences in clinical outcome?

<p>Abstract</p> <p>Background</p> <p>Ethnic differences in clinical outcome after percutaneous coronary intervention (PCI) have been reported. Data within different Asian subpopulations is scarce. We aim to explore the differences in clinical profile and outcome between Chinese, Malay and Indian Asian patients who undergo PCI for coronary artery disease (CAD).</p> <p>Methods</p> <p>A prospective registry of consecutive patients undergoing PCI from January 2002 to December 2007 at a tertiary care center was analyzed. Primary endpoint was major adverse cardiovascular events (MACE) of myocardial infarction (MI), repeat revascularization and all-cause death at six months.</p> <p>Results</p> <p>7889 patients underwent PCI; 7544 (96%) patients completed follow-up and were included in the analysis (79% males with mean age of 59 years ± 11). There were 5130 (68%) Chinese, 1056 (14%) Malays and 1001 (13.3%) Indian patients. The remaining 357 (4.7%) patients from other minority ethnic groups were excluded from the analysis. The primary end-point occurred in 684 (9.1%) patients at six months. Indians had the highest rates of six month MACE compared to Chinese and Malays (Indians 12% vs. Chinese 8.2% vs. Malays 10.7%; OR 1.55 95%CI 1.24-1.93, p < 0.001). This was contributed by increased rates of MI (Indians 1.9% vs. Chinese 0.9% vs. Malays 1.3%; OR 4.49 95%CI 1.91-10.56 p = 0.001), repeat revascularization (Indians 6.5% vs. Chinese 4.1% vs. Malays 5.1%; OR 1.64 95%CI 1.22-2.21 p = 0.0012) and death (Indians 11.4% vs. Chinese 7.6% vs. Malays 9.9%; OR 1.65 95%CI 1.23-2.20 p = 0.001) amongst Indian patients.</p> <p>Conclusion</p> <p>These data indicate that ethnic variations in clinical outcome exist following PCI. In particular, Indian patients have higher six month event rates compared to Chinese and Malays. Future studies are warranted to elucidate the underlying mechanisms behind these variations.</p

Normal Values of Myocardial Deformation Assessed by Cardiovascular Magnetic Resonance Feature Tracking in a Healthy Chinese Population: A Multicenter Study

Reference values on atrial and ventricular strain from cardiovascular magnetic resonance (CMR) are essential in identifying patients with impaired atrial and ventricular function. However, reference values have not been established for Chinese subjects. One hundred and fifty healthy volunteers (75 Males/75 Females; 18–82 years) were recruited. All underwent CMR scans with images acceptable for further strain analysis. Subjects were stratified by age: Group 1, 18–44 years; Group 2, 45–59 years; Group 3, ≥60 years. Feature tracking of CMR cine imaging was used to obtain left atrial global longitudinal (LA Ell) and circumferential strains (LA Ecc) and respective systolic strain rates, left ventricular longitudinal (LV Ell), circumferential (LV Ecc) and radial strains (LV Err) and their respective strain rates, and right ventricular longitudinal strain (RV Ell) and strain rate. LA Ell and LA Ecc were 32.8 ± 9.2% and 40.3 ± 13.4%, respectively, and RV Ell was −29.3 ± 6.0%. LV Ell, LV Ecc and LV Err were −22.4 ± 2.9%, −24.3 ± 3.1%, and 79.0 ± 19.4%, respectively. LV Ell and LV Ecc were higher in females than males (P &lt; 0.05). LA Ell, LA Ecc, and LV Ecc decreased, while LV Err increased with age (P &lt; 0.05). LV Ell and RV Ell were not shown to be associated with age. Normal ranges for atrial and ventricular strain and strain rates are provided using CMR feature tracking in Chinese subjects

Factors associated with nursing home placement of all patients admitted for inpatient rehabilitation in Singapore community hospitals from 1996 to 2005: A disease stratified analysis

10.1371/journal.pone.0082697PLoS ONE812-POLN

Mapping infectious disease hospital surge threats to lessons learnt in Singapore: a systems analysis and development of a framework to inform how to DECIDE on planning and response strategies.

BACKGROUND: Hospital usage and service demand during an Infectious Disease (ID) outbreak can tax the health system in different ways. Herein we conceptualize hospital surge elements, and lessons learnt from such events, to help build appropriately matched responses to future ID surge threats. METHODS: We used the Interpretive Descriptive qualitative approach. Interviews (n = 35) were conducted with governance and public health specialists; hospital based staff; and General Practitioners. Key policy literature in tandem with the interview data were used to iteratively generate a Hospital ID Surge framework. We anchored our narrative account within this framework, which is used to structure our analysis. RESULTS: A spectrum of surge threats from combinations of capacity (for crowding) and capability (for treatment complexity) demands were identified. Starting with the Pyramid scenario, or an influx of high screening rates flooding Emergency Departments, alongside fewer and manageable admissions; the Reverse-Pyramid occurs when few cases are screened and admitted but those that are, are complex; during a 'Black' scenario, the system is overburdened by both crowding and complexity. The Singapore hospital system is highly adapted to crowding, functioning remarkably well at constant near-full capacity in Peacetime and resilient to Endemic surges. We catalogue 26 strategies from lessons learnt relating to staffing, space, supplies and systems, crystalizing institutional memory. The DECIDE model advocates linking these strategies to types of surge threats and offers a step-by-step guide for coordinating outbreak planning and response. CONCLUSIONS: Lack of a shared definition and decision making of surge threats had rendered the procedures somewhat duplicative. This burden was paradoxically exacerbated by a health system that highly prizes planning and forward thinking, but worked largely in silo until an ID crisis hit. Many such lessons can be put into play to further strengthen our current hospital governance and adapted to more diverse settings

HIF1α drives chemokine factor pro-tumoral signaling pathways in acute myeloid leukemia

Approximately 80% of patients diagnosed with acute myeloid leukemia (AML) die as a consequence of failure to eradicate the tumor from the bone marrow microenvironment. We have recently shown that stroma-derived interleukin-8 (IL-8) promotes AML growth and survival in the bone marrow in response to AML-derived macrophage migration inhibitory factor (MIF). In the present study we show that high constitutive expression of MIF in AML blasts in the bone marrow is hypoxia-driven and, through knockdown of MIF, HIF1α and HIF2α, establish that hypoxia supports AML tumor proliferation through HIF1α signaling. In vivo targeting of leukemic cell HIF1α inhibits AML proliferation in the tumor microenvironment through transcriptional regulation of MIF, but inhibition of HIF2α had no measurable effect on AML blast survival. Functionally, targeted inhibition of MIF in vivo improves survival in models of AML. Here we present a mechanism linking HIF1α to a pro-tumoral chemokine factor signaling pathway and in doing so, we establish a potential strategy to target AML

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer