Subjective Assessment Underestimates Fraility in Patients With Heart Failure Referred for Advanced Therapies.

Assessment of frailty is key for evaluation for advanced therapies (ATs). Most programs use a subjective provider assessment (SPA) or "eye-ball" test; however, objective measures exist. The modified five-item Fried Frailty Index (mFFI) is a validated tool to assess frailty. We compared SPA to mFFI testing in patients referred for AT. We also compared levels of macrophage migration inhibitory factor (MIF), an inflammatory biomarker associated with worse outcomes in heart failure, between frail and not frail subjects. Seventy-eight patients referred for evaluation for AT underwent both SPA and mFFI testing. Three cardiac surgeons independently assessed patients for frailty (SPA). SPA significantly underestimated frailty compared with mFFI testing and correlation between SPA and mFFI was not strong (κ = 0.02-0.14). Providers were correct 84% of the time designating a subject as frail, but only 40% of the time designating as not frail. Agreement between all three providers was robust (76%), which was primarily driven by designation as not frail. There was no significant difference in plasma MIF levels between frail and not frail subjects (47.6 ± 25.2 vs . 45.2 ± 18.9 ng/ml; p = 0.6). Clinicians significantly underestimate frailty but are usually correct when designating a patient as frail.

Assessment of cardiac recovery in patients supported with venoarterial extracorporeal membrane oxygenation.

AIMS: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used to support patients in cardiogenic shock (CS). Early determination of disposition is paramount, as longer durations of support have been associated with worse outcomes. We describe a stepwise, bedside weaning protocol to assess cardiopulmonary recovery during VA-ECMO. METHODS AND RESULTS: Over 1 year, we considered all patients on VA-ECMO for CS for the Weaning Protocol (WP) at our centre. During the WP, patients had invasive haemodynamic monitoring, echocardiography, and blood gas analysis while flow was reduced in 1 LPM decrements. Ultimately, the circuit was clamped for 30 min, and final measures were taken. Patients were described as having durable recovery (DR) if they were free of pharmacological and mechanical support at 30 days post-decannulation. Over 12 months, 34 patients had VA-ECMO for CS. Fourteen patients were eligible for the WP at 4-12 days. Ten patients tolerated full flow reduction and were successfully decannulated. Twenty-four per cent of the entire cohort demonstrated DR with no adverse events during the WP. Patients with DR had significantly higher ejection fraction, cardiac index, and smaller left ventricular size at lowest flow during the WP. CONCLUSIONS: We describe a safe, stepwise, bedside weaning protocol to assess cardiac recovery during VA-ECMO. Early identification of patients more likely to recover may improve outcomes during ECMO support.

A metaproteomic approach to study human-microbial ecosystems at the mucosal luminal interface.

Aberrant interactions between the host and the intestinal bacteria are thought to contribute to the pathogenesis of many digestive diseases. However, studying the complex ecosystem at the human mucosal-luminal interface (MLI) is challenging and requires an integrative systems biology approach. Therefore, we developed a novel method integrating lavage sampling of the human mucosal surface, high-throughput proteomics, and a unique suite of bioinformatic and statistical analyses. Shotgun proteomic analysis of secreted proteins recovered from the MLI confirmed the presence of both human and bacterial components. To profile the MLI metaproteome, we collected 205 mucosal lavage samples from 38 healthy subjects, and subjected them to high-throughput proteomics. The spectral data were subjected to a rigorous data processing pipeline to optimize suitability for quantitation and analysis, and then were evaluated using a set of biostatistical tools. Compared to the mucosal transcriptome, the MLI metaproteome was enriched for extracellular proteins involved in response to stimulus and immune system processes. Analysis of the metaproteome revealed significant individual-related as well as anatomic region-related (biogeographic) features. Quantitative shotgun proteomics established the identity and confirmed the biogeographic association of 49 proteins (including 3 functional protein networks) demarcating the proximal and distal colon. This robust and integrated proteomic approach is thus effective for identifying functional features of the human mucosal ecosystem, and a fresh understanding of the basic biology and disease processes at the MLI.

RANTES: a genetic risk marker for multiple sclerosis.

UNLABELLED: Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a beta-chemokine and has been detected in brain lesions of multiple sclerosis (MS) patients. Considering its potential role in MS, we screened two functional polymorphisms in the proximal promoter region of the RANTES in MS patients versus controls. METHODS: We examined 140 postmortem brain samples from subjects with a primary diagnosis of MS, and peripheral blood samples from 216 control subjects. The RANTES-28C/G and -403G/A promoter polymorphisms were examined. All subjects were non-Hispanic Caucasians. RESULTS: MS cases differed from controls showing a significant association with the 403G/A polymorphism (odds ratio, 2.359, [1.465-3.799]; P=0.0001), but not the -28C/G (P=NS) polymorphism. There was a significant association of the -28G allele with both early onset (P=0.031) and longer survival (P=0.006). CONCLUSION: There is a significant but complex association of the RANTES gene with MS.