Liberal transfusion strategy improves survival in perioperative but not in critically ill patients. A meta-analysis of randomised trials

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Assessment of surgeon communication skills from the patient perspective: A national evaluation using the Communication Assessment Tool

Objective: The Communication Assessment Tool (CAT) has previously been translated and adapted to the Italian context. This national study aimed to validate the CAT and evaluate communication skills of practicing surgeons from the patient perspective. Methods: CAT consists of 14 items associated with a 5-point scale (5 = excellent); results are reported as the percent of ‘‘excellent’’ scores. It was administered to 920 consenting outpatients aged 18–84 in 26 Italian surgical departments. Results: The largest age group was 45–64 (43.8%); 52.2% of the sample was male. Scores ranged from 44.6% to 66.6% excellent. The highest-scoring items were “Treated me with respect” (66.6%), “Gave me as much information as I wanted” (66.3%) and “Talked in terms I could understand” (66.0%); the lowest was “Encouraged me to ask questions” (44.6%). Significant differences were associated with age (18–24 year old patients exhibited the lowest scores) and geographical location (Northern Italy had the highest scores). Conclusion: CAT is a valid tool for measuring communication in surgical settings. Practice Implications: Results suggest that expectations of young people for communication in surgical settings are not being met. While there is room to improve communication skills of surgeons across Italy, patients highlighted the greatest need in the Central and Southern regions

Management of Bleeding and Hemolysis During Percutaneous Microaxial Flow Pump Support A Practical Approach

© 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Percutaneous ventricular assist devices (pVADs) are increasingly being used because of improved experience and availability. The Impella (Abiomed), a percutaneous microaxial, continuous-flow, short-term ventricular assist device, requires meticulous postimplantation management to avoid the 2 most frequent complications, namely, bleeding and hemolysis. A standardized approach to the prevention, detection, and treatment of these complications is mandatory to improve outcomes. The risk for hemolysis is mostly influenced by pump instability, resulting from patient- or device-related factors. Upfront echocardiographic assessment, frequent monitoring, and prompt intervention are essential. The precarious hemostatic balance during pVAD support results from the combination of a procoagulant state, due to critical illness and contact pathway activation, together with a variety of factors aggravating bleeding risk. Preventive strategies and appropriate management, adapted to the impact of the bleeding, are crucial. This review offers a guide to physicians to tackle these device-related complications in this critically ill pVAD-supported patient population.Peer reviewe

Impedance Responses Reveal β2-Adrenergic Receptor Signaling Pluridimensionality and Allow Classification of Ligands with Distinct Signaling Profiles

The discovery that drugs targeting a single G protein-coupled receptor (GPCR) can differentially modulate distinct subsets of the receptor signaling repertoire has created a challenge for drug discovery at these important therapeutic targets. Here, we demonstrate that a single label-free assay based on cellular impedance provides a real-time integration of multiple signaling events engaged upon GPCR activation. Stimulation of the β2-adrenergic receptor (β2AR) in living cells with the prototypical agonist isoproterenol generated a complex, multi-featured impedance response over time. Selective pharmacological inhibition of specific arms of the β2AR signaling network revealed the differential contribution of Gs-, Gi- and Gβγ-dependent signaling events, including activation of the canonical cAMP and ERK1/2 pathways, to specific components of the impedance response. Further dissection revealed the essential role of intracellular Ca2+ in the impedance response and led to the discovery of a novel β2AR-promoted Ca2+ mobilization event. Recognizing that impedance responses provide an integrative assessment of ligand activity, we screened a collection of β-adrenergic ligands to determine if differences in the signaling repertoire engaged by compounds would lead to distinct impedance signatures. An unsupervised clustering analysis of the impedance responses revealed the existence of 5 distinct compound classes, revealing a richer signaling texture than previously recognized for this receptor. Taken together, these data indicate that the pluridimensionality of GPCR signaling can be captured using integrative approaches to provide a comprehensive readout of drug activity

2019 EACTS Expert Consensus on long-term mechanical circulatory support

Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many-sometimes contradictory-observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Lipid and protein composition of Niemann-Pick type A brain rafts

Lipid rafts, or DRM (Detergent Resistant Membrane) are supermolecular organizations created by lateral spontaneous segregation of specific lipids (particularly sphingolipids and cholesterol) and proteins in restricted areas of the plasma membrane. They represent structural and functional units involved in different pathways of signalling and in cellular adhesion [2]. In the nervous system, they are involved in normal cell functions and in the pathogenesis of neurodegenerative diseases. In fact, alterations of molecular composition and organization within DRM have been related to these pathological events. This hypothesis is based on two important observations: the first one is that certain proteins, whose transformation in aberrant isoforms causes the onset of neuronal pathologies, are enriched in these domains (for example, the amyloid precursor protein and the prion protein); the second one regards the fact that numerous neurodegenerative diseases show altered sphingolipid metabolism. The relatively large number of papers dedicated to the preparation of a lipid domain fraction from brain or brain substructures obviously reflects the interest for the supposed role of lipid domains in neuronal development and in the pathogenesis of neurodegenerative diseases [3]. However, studies on DRM have been carried out mainly using cell cultures and the suitability of methods for the preparation of DRM fractions from brain tissues has never been systematically defined. The cellular approach is important and useful when we want to study the structural and biochemical properties of DRM isolated from specific cellular types, reducing as much as possible the contamination by other cells, but this model is very simplified and reductive to study the effects of neurodegeneration on DRM in the brain. In fact, it is known that neurodegeneration involves more than one cellular type and can cause the loss of neurons, demyelination events or changes in the structure of the whole cerebral tissue. We set up an experimental condition for the preparation of a sphingolipid- and cholesterol-enriched membrane fraction from mouse brain. To reach this result we performed several DRM preparations starting from a brain lysate prepared varying only the ratio between the protein and the detergent content and maintaining unaltered all the other parameters. For all the experimental conditions assayed we worked at 4\ub0C in presence of Triton X-100, as detergent, at a final concentration of 1%. Starting from different conditions of brain lysis the effects on the DRM preparation have been carefully checked by a detailed characterization of lipid and protein content of the low density fractions obtained and we could define a restricted range of values for which it has been possible to effectively isolate a low density fraction characterized by a protein and lipid content and by relative enrichments typical of the so called DRM. Once this procedure has been set up, we tried to apply it on an available model of neurodegenerative disease. This model consists in an acid sphingomyelinase knockout mouse (ASMKO), which develops a neurodegenerative pathology resembling the human Niemann-Pick type A disease. These mice accumulate sphingomyelin in the reticuloendothelial system of liver, spleen, bone marrow and lung and in the brain. First of all, we did a comparative study of the lipid and protein composition of wild type (WT) and ASMKO brain at different time of development. Since sphingomyelin is one of the main components of lipid rafts, we analysed how the composition of these Niemann-Pick A brain rafts changed, as a consequence of the highly increased amount of sphingomyelin