AimsTo evaluate the effect of iron deficiency (ID) and/or anaemia on health-related quality of life (HRQoL) in patients with chronic heart failure (CHF).Methods and resultsWe undertook a post-hoc analysis of a cohort of CHF patients in a single-centre study evaluating cognitive function. At recruitment, patients provided baseline information and completed the Minnesota Living with Heart Failure questionnaire (MLHFQ) for HRQoL (higher scores reflect worse HRQoL). At the same time, blood samples were taken for serological evaluation. ID was defined as serum ferritin levels <100 ng/mL or serum ferritin <800 ng/mL with transferrin saturation <20%. Anaemia was defined as haemoglobin ≤12 g/dL. A total of 552 CHF patients were eligible for inclusion, with an average age of 72 years and 40% in NYHA class III or IV. The MLHFQ overall summary scores were 41.0 ± 24.7 among those with ID, vs. 34.4 ± 26.4 for non-ID patients (P = 0.003), indicating worse HRQoL. When adjusted for other factors associated with HRQoL, ID was significantly associated with worse MLHFQ overall summary (P = 0.008) and physical dimension scores (P = 0.002), whereas anaemia was not (both P > 0.05). Increased levels of soluble transferrin receptor were also associated with impaired HRQoL (P ≤ 0.001). Adjusting for haemoglobin and C-reactive protein, ID was more pronounced in patients with anaemia compared with those without (P < 0.001).ConclusionIn patients with CHF, ID but not anaemia was associated with reduced HRQoL, mostly due to physical factors.

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We demonstrate that AlphaFold and AlphaFold Multimer, implemented within the ColabFold suite, can accurately predict the structures of the furin enzyme with known six residue inhibitory peptides. Noting the similarity of the peptide inhibitors to polybasic furin cleavage domain insertion region of the SARS-CoV-2, which begins at P681, we implement this approach to study the wild type furin cleavage domain for the virus and several mutants. We introduce mutations in silico for alpha, omicron, and delta variants, for several sequences which have been rarely observed, for sequences which have not yet been observed, for other coronaviruses (NL63, OC43, HUK1a, HUK1b, MERS, and 229E), and for the H5N1 flu. We show that interfacial hydrogen bonds between the furin cleavage domain and furin are a good measure of binding strength that correlate well with endpoint binding free energy estimates, and conclude that among all candidate viral sequences studied, delta is near the very top binding strength within statistical accuracy. However, the binding strength of several rare sequences match delta within statistical accuracy. We find that the furin S1 pocket is optimized for binding arginine as opposed to lysine. This residue, typically at sequence position five, contains the most hydrogen bonds to the furin, and hydrogen bond count for just this residue shows a strong positive correlation with the overall hydrogen bond count . We demonstrate that the root mean square backbone C-alpha fluctuation of the first residue in the furin cleavage domain has a strong negative correlation with the interfacial hydrogen bond count. We show by considering the variation with the number of basic residues that the maximum mean number of interfacial hydrogen bonds expected is 15.7 at 4 basic residues.

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Introduction: Growing availability of advanced imaging studies (AdIS) has resulted in increasing use of studies other than non-contrast CT (NCCT) in the evaluation of acute ischemic stroke (AIS) patients. The diagnosis of AIS is mainly clinical, and thrombolysis in patients with stroke mimics is generally considered to be safe. However, the need for diagnostic certainty and timely detection of large vessel occlusion (LVO) may incline physicians to perform more AdIS. Hypothesis: Performing pre-treatment AdIS in all patients with AIS will prolong DNT without conferring clear benefits regarding treatment decisions. Methods: We reviewed a prospective registry of AIS patients arriving at the Neurologic Emergency Department. We obtained additional information from the patients’ clinical records, and all pertinent imaging studies were reviewed to confirm diagnosis and site of arterial occlusion. Results: We analyzed 128 AIS patients treated with IV thrombolysis. Mean Door to-Needle-Time (DNT) was 83 min. Only 46% of patients were thrombolysed in the first 60 minutes after arrival. AdIS were performed in 60 patients (48%) They were equally performed among patients with NIHSS scores below and above 10 points, a possible cutoff for the presence of LVO. They also were performed equally in patients with clinically mild, and severe strokes, when the clinical diagnosis of AIS was not in doubt. On bivariate analysis, factors associated with DNT<60 minutes were: female sex, posterior circulation stroke and whether only NCCT was performed. Exclusive use of NCCT was associated with a higher percentage of DNT<60 minutes (59 vs 34%, p=0.005). On multivariable analysis, NCCT use was independently associated with DNT<60 min (OR= 2.92, p<0.007) Regarding different imaging studies, DNT means were as follows: NCCT: 69 min, CTA:79 min, CTP: 125 min, MRI 108 min (Difference between groups p=0.007). No patients were excluded from thrombolytic treatment based on AdIS results. Conclusions: The pre-thrombolysis performance of AdIS carries the risk of prolonging DNT and lowering the possibility of benefit for AIS patients. Selection of patients for specific studies and deferring AdIS until after initiating alteplase should be pursued.

Background: Acute coronary syndrome (ACS) is the first cause of mortality in Colombia. An erroneous risk stratification, in the emergency room (ER), affects the interventions performed and the rate of major cardiovascular adverse events. We measured the difference in GRACE score and stratification of coronary risk, by using the results of troponins measured sequentially during initial care. Methods: With a retrospective descriptive design, clinical records of patients treated for precordial pain of ≥ intermediate probability for ACS were evaluated, without indication of immediate invasive management, attended in the ER of a clinic of the third level of Bogotá, during 2017. Determined the difference between the GRACE score calculated with the first (GRACE-1), second (GRACE-2) or troponin delta (GRACE-delta) [paired T-test], and the proportion of poorly stratified patients was measured when using the first troponin [X2, Z-score]. Results: 44 patients in a period of 6 months were identified. The majority men, older adults, middle age 73 years. The average (SD) of scores GRACE-1, GRACE-2 and GRACE-delta, was 114.14 (30.73), 115.55 (30.14) and 111.11 (28.79), respectively; when comparing GRACE-delta with GRACE-1 and GRACE-2 significant differences were identified (p: <0.05). Error in the stratification of coronary risk was identified in 10/44 patients (22.7%), and 9/44 (20.4%) presented over-stratification. Conclusion: The stratification of coronary risk using the first troponin, unlike the troponin delta (item not clarified in the guidelines), evidenced an over-stratification in at least 20% of the patients, establishing the need for more invasive procedures and possibly longer hospital stay.