Persistent pulmonary congestion before discharge predicts rehospitalization in heart failure: a lung ultrasound study

BACKGROUND: B-lines evaluated by lung ultrasound (LUS) are the sonographic sign of pulmonary congestion, a major predictor of morbidity and mortality in patients with heart failure (HF). Our aim was to assess the prognostic value of B-lines at discharge to predict rehospitalization at 6 months in patients with acute HF (AHF). METHODS: A prospective cohort of 100 patients admitted to a Cardiology Department for dyspnea and/or clinical suspicion of AHF were enrolled (mean age 70 ± 11 years). B-lines were evaluated at admission and before discharge. Subjects were followed-up for 6-months after discharge. RESULTS: Mean B-lines at admission was 48 ± 48 with a statistically significant reduction before discharge (20 ± 23, p 15) (log rank χ(2) 20.5, p 15 before discharge (hazard ratio [HR] 11.74; 95 % confidence interval [CI] 1.30-106.16) was an independent predictor of events at 6 months. CONCLUSIONS: Persistent pulmonary congestion before discharge evaluated by ultrasound strongly predicts rehospitalization for HF at 6-months. Absence or a mild degree of B-lines identify a subgroup at extremely low risk to be readmitted for HF decompensation

PEGylation Promotes Hemoglobin Tetramer Dissociation

Hemoglobin conjugated with poly(ethylene glycol) (PEG) acts as an oxygen carrier free in plasma, substituting red blood cells in supplementing oxygen in hypo-oxygenation pathologies. Given the complexity of oxygen delivery controls, subtle structural and functional differences in PEGylated hemoglobins might be associated with distinct physiological responses and, potentially, adverse effects. We have compared hemoglobin PEGylated under anaerobic conditions, called PEG-Hb(deoxy), with hemoglobin PEGylated under aerobic conditions, called PEG-Hb(oxy), a product that mimics Hemospan, produced by Sangart, Inc. SDS PAGE and MALDI-TOF analyses demonstrated that PEG conjugation yields products characterized by a broad distribution of PEG/hemoglobin ratios. The elution profiles in size-exclusion chromatography indicate that both products exhibit a more homogeneous distribution of molecular weight/hydrodynamic volume under deoxy conditions and at higher concentrations. PEG-Hb(oxy) shows high oxygen affinity, low modulation of allosteric effectors, almost no cooperativity, a fast and monophasic CO binding, and a limited dependence of functional properties on concentration, whereas PEG-Hb(deoxy) exhibits oxygen binding curves that significantly depend on protein concentration, and a slow CO binding, similar to native hemoglobin. PEGylated CO-hemoglobins, probed by flash photolysis, exhibited a lower amplitude for the geminate rebinding phase with respect to native hemoglobin and a negligible T state bimolecular CO rebinding phase. These findings are explained by an increased dissociation of PEGylated hemoglobins into dimers and perturbed T and R states with decreased quaternary transition rates. These features are more pronounced for PEG-Hb(oxy) than PEG-Hb(deoxy). The detected heterogeneity might be a source of adverse effects when PEGylated Hbs are used as blood substitutes

Pulmonary arterial hypertension and interstitial lung fibrosis in systemic sclerosis: One-stop shop assessment with cardiac and chest ultrasound

Background: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are common complications of systemic sclerosis (SSc). Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC), i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILD and PAH by integrated cardiac and chest ultrasound in SSc. Materials and methods: We enrolled 30 consecutive SSc patients (age=54?13 years, 23 females) in the Rheumatology Clinic of Pisa University. In all, we assessed Systolic Pulmonary Arterial Pressure (SPAP), from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space). All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70), associated with development of pulmonary fibrosis. Twenty-eight patients also underwent High Resolution Computed Tomography, HRCT (from 0=no fibrosis to 3=honey combing). Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence SSc-70 antibodies (see figure). ULC number was similar in localized or diffuse forms (16?20 vs. 21?19, p=ns) and was unrelated to SPAP (r=0.216, p=ns). Conclusions: Cardiac and chest sonography assessment of SPAP and ULC allow a complete, simple, radiation-free characterization of vascular and interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number, but not SPAP, is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies

Lung ultrasound: a new tool for the cardiologist

For many years the lung has been considered off-limits for ultrasound. However, it has been recently shown that lung ultrasound (LUS) may represent a useful tool for the evaluation of many pulmonary conditions in cardiovascular disease. The main application of LUS for the cardiologist is the assessment of B-lines. B-lines are reverberation artifacts, originating from water-thickened pulmonary interlobular septa. Multiple B-lines are present in pulmonary congestion, and may help in the detection, semiquantification and monitoring of extravascular lung water, in the differential diagnosis of dyspnea, and in the prognostic stratification of chronic heart failure and acute coronary syndromes

[Ultrasound lung comets: new echographic sign of lung interstitial fibrosis in systemic sclerosis].

Objective: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are common complications of systemic sclerosis (SSc). Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC), i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILaD and PAH by integrated cardiac and chest ultrasound in SSc. Methods: We enrolled 30 consecutive SSc patients (age= 54±13 years, 23 females) in the Rheumatology Clinic of Pisa University. In all, we assessed systolic pulmonary arterial pressure (SPAP), from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space). All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70), and antiicentromere associated with development of pulmonary involvement. Twenty-eight patients also underwent high resolution computed tomography, HRCT (from 0= no fibrosis to 3= honey combing). Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence Scl-70 antibodies. ULC number was similar in localized or diffuse forms (16±20 vs 21±19, p=ns) and was unrelated to SPAP (r=0.216, p=ns). Conclusions: Chest sonography assessment and ULC allow a complete, simple, radiation-free characterization of interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies

Chest sonography: a useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome

<p>Abstract</p> <p>Background</p> <p>Differential diagnosis between acute cardiogenic pulmonary edema (APE) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) may often be difficult. We evaluated the ability of chest sonography in the identification of characteristic pleuropulmonary signs useful in the diagnosis of ALI/ARDS and APE.</p> <p>Methods</p> <p>Chest sonography was performed on admission to the intensive care unit in 58 consecutive patients affected by ALI/ARDS or by acute pulmonary edema (APE).</p> <p>Results</p> <p>Ultrasound examination was focalised on finding in the two groups the presence of: 1) alveolar-interstitial syndrome (AIS) 2) pleural lines abnormalities 3) absence or reduction of "gliding" sign 4) "spared areas" 5) consolidations 6) pleural effusion 7) "lung pulse".</p> <p>AIS was found in 100% of patients with ALI/ARDS and in 100% of patients with APE (p = ns). Pleural line abnormalities were observed in 100% of patients with ALI/ARDS and in 25% of patients with APE (p < 0.0001). Absence or reduction of the 'gliding sign' was observed in 100% of patients with ALI/ARDS and in 0% of patients with APE. 'Spared areas' were observed in 100% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001). Consolidations were present in 83.3% of patients with ALI/ARDS in 0% of patients with APE (p < 0.0001). A pleural effusion was present in 66.6% of patients with ALI/ARDS and in 95% of patients with APE (p < 0.004). 'Lung pulse' was observed in 50% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001).</p> <p>All signs, except the presence of AIS, presented a statistically significant difference in presentation between the two syndromes resulting specific for the ultrasonographic characterization of ALI/ARDS.</p> <p>Conclusion</p> <p>Pleuroparenchimal patterns in ALI/ARDS do find a characterization through ultrasonographic lung scan. In the critically ill the ultrasound demonstration of a dyshomogeneous AIS with spared areas, pleural line modifications and lung consolidations is strongly predictive, in an early phase, of non-cardiogenic pulmonary edema.</p

Development and implementation of the AIDA international registry for patients with non-infectious uveitis

Introduction: The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU). Methods: This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform. Results: Ninety-five centres have been involved from 19 countries and four continents from 24&nbsp;March to 16&nbsp;November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient’s demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU. Conclusions: The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide

A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide Multi-Center Retrospective Observational Study.

Background: Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis. Objectives: To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults. Methods: We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016. Results: Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two (32.1%) patients had been treated with both agents. IL-1 inhibitors were employed in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors were associated with corticosteroids in 285 (54.18%) courses and disease modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from 30 to 200 mg/day (or 1.0-2.0 mg/kg/day) among adults and 2-4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150mg every 8 weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was higher among patients treated with ANA at a dosage of 100 mg/day than those treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after the age of 65 compared to both children and patients aged between 16 and 65 (p = 0.003 and p = 0.03, respectively). Conclusions: IL-1 inhibitors are mostly used off-label, especially ANA, during adulthood. The high frequency of good clinical responses suggests that IL-1 inhibitors are used with awareness of pathogenetic mechanisms; adult healthcare physicians generally employ standard dosages, while pediatricians are more prone in using a weight-based posology. Dose adjustments and switching between different agents showed to be effective treatment strategies. Our data confirm the good safety profile of IL-1 inhibitors

Development and Implementation of the AIDA International Registry for Patients With Undifferentiated Systemic AutoInflammatory Diseases

Objective: This paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs). Methods: This is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research. The instrument is endowed with flexibility, and it could change over time according to the scientific acquisitions and potentially communicate with other similar tools; this platform ensures security, data quality and data governance. Results: The focus of the AIDA project is connecting physicians and researchers from all over the world to shed a new light on heterogeneous rare diseases. Since its birth, 110 centers from 23 countries and 4 continents have joined the AIDA project. Fifty-four centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 179 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry is collecting baseline and follow-up data using 3,769 fields organized into 23 instruments, which include demographics, history, symptoms, trigger/risk factors, therapies, and healthcare information access for USAIDs patients. Conclusions: The development of the AIDA International Registry for USAIDs patients will facilitate the online collection of real standardized data, connecting a worldwide group of researchers: the Registry constitutes an international multicentre observational groundwork aimed at increasing the patient cohort of USAIDs in order to improve our knowledge of this peculiar cluster of autoinflammatory diseases. NCT 05200715 available at https://clinicaltrials.gov/