Anakinra Therapy for Non-cancer Inflammatory Diseases

Interleukin-1 (IL-1) is the prototypical inflammatory cytokine: two distinct ligands (IL-1α and IL-1β) bind the IL-1 type 1 receptor (IL-1R1) and induce a myriad of secondary inflammatory mediators, including prostaglandins, cytokines, and chemokines. IL-1α is constitutively present in endothelial and epithelial cells, whereas IL-1β is inducible in myeloid cells and released following cleavage by caspase-1. Over the past 30 years, IL-1-mediated inflammation has been established in a broad spectrum of diseases, ranging from rare autoinflammatory diseases to common conditions such as gout and rheumatoid arthritis (RA), type 2 diabetes, atherosclerosis, and acute myocardial infarction. Blocking IL-1 entered the clinical arena with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist (IL-1Ra); IL-1Ra prevents the binding of IL-1α as well as IL-1β to IL-1R1. Quenching IL-1-mediated inflammation prevents the detrimental consequences of tissue damage and organ dysfunction. Although anakinra is presently approved for the treatment of RA and cryopyrin-associated periodic syndromes, off-label use of anakinra far exceeds its approved indications. Dosing of 100 mg of anakinra subcutaneously provides clinically evident benefits within days and for some diseases, anakinra has been used daily for over 12 years. Compared to other biologics, anakinra has an unparalleled record of safety: opportunistic infections, particularly Mycobacterium tuberculosis, are rare even in populations at risk for reactivation of latent infections. Because of this excellent safety profile and relative short duration of action, anakinra can also be used as a diagnostic tool for undefined diseases mediated by IL-1. Although anakinra is presently in clinical trials to treat cancer, this review focuses on anakinra treatment of acute as well as chronic inflammatory diseases

Carbon footprint of forest operations under different management regimes

Different forest management regimes have different carbon footprints due to alternative op- erational strategies and options. Data concerning CO2 emissions (kg m–3) in felling, extraction, comminution and transport operations, performed under two different forest management regime (close-to-nature and plantation), were collected through a systematic literature review involving 162 scientific papers and compiled into a database. Results show that, within limits, forest operations in plantations produce lower emissions due to easier operational conditions, while transportation in both close-to-nature and plantation based forest operations reported the highest levels of emissions. Literature came from a variety of sources and often differed in context due to factors such as technology, work technique, operator skill and environmental conditions. These factors have been shown to highly affect the results obtained from the stud- ies. Nevertheless, it has been possible to summarize most of the information gathered and to highlight the most representative driving factors in CO2 emissions throughout different forest management regime

Carbon Footprint of Forest Operations under Different Management Regimes

Different forest management regimes have different carbon footprints due to alternative operational strategies and options. Data concerning CO2 emissions (kg m–3) in felling, extraction, comminution and transport operations, performed under two different forest management regime (close-to-nature and plantation), were collected through a systematic literature review involving 162 scientific papers and compiled into a database. Results show that, within limits, forest operations in plantations produce lower emissions due to easier operational conditions, while transportation in both close-to-nature and plantation based forest operations reported the highest levels of emissions. Literature came from a variety of sources and often differed in context due to factors such as technology, work technique, operator skill and environmental conditions. These factors have been shown to highly affect the results obtained from the studies. Nevertheless, it has been possible to summarize most of the information gathered and to highlight the most representative driving factors in CO2 emissions throughout different forest management regimes

Carbon Footprint of Forest Operations under Different Management Regimes

Different forest management regimes have different carbon footprints due to alternative operational strategies and options. Data concerning CO2 emissions (kg m–3) in felling, extraction, comminution and transport operations, performed under two different forest management regime (close-to-nature and plantation), were collected through a systematic literature review involving 162 scientific papers and compiled into a database. Results show that, within limits, forest operations in plantations produce lower emissions due to easier operational conditions, while transportation in both close-to-nature and plantation based forest operations reported the highest levels of emissions. Literature came from a variety of sources and often differed in context due to factors such as technology, work technique, operator skill and environmental conditions. These factors have been shown to highly affect the results obtained from the studies. Nevertheless, it has been possible to summarize most of the information gathered and to highlight the most representative driving factors in CO2 emissions throughout different forest management regimes

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The Role of Extracorporeal Membrane Oxygenation Support after Pulmonary Thrombo-Endarterectomy

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare consequence of acute or chronic pulmonary embolism. Pulmonary endarterectomy (PEA) is the gold standard treatment: expert centers are able to offer this challenging procedure with low in-hospital mortality, excellent hemodynamic results, and significant improvement in exercise tolerance and quality of life. Despite careful preoperative selection and increasing technical experience in PEA, some patients may suffer from life-threatening complications requiring extracorporeal life support (ECLS). ECLS is necessary in case of heart failure, respiratory failure, or both. According to different indications and timing, cardiopulmonary failure after PEA should be managed with a tailored approach: veno-venous or veno-arterial support, and central or peripheral cannulation. In the present chapter, causes, management strategies, and outcomes of perioperative ECLS for PEA are discussed

Therapeutic alternatives in chronic thromboembolic pulmonary hypertension: from pulmonary endarterectomy to balloon pulmonary angioplasty to medical therapy. State of the art from a multidisciplinary team

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with a very complex pathophysiology differing from other causes of pulmonary hypertension (PH). It is an infrequent consequence of acute pulmonary embolism that is frequently misdiagnosed. Pathogenesis has been related to coagulation abnormalities, infection or inflammation, although these disturbances can be absent in many cases. The hallmarks of CTEPH are thrombotic occlusion of pulmonary vessels, variable degree of ventricular dysfunction and secondary microvascular arteriopathy. The definition of CTEPH also includes an increase in mean pulmonary arterial pressure of more than 25 mmHg with a normal pulmonary capillary wedge of less than 15 mmHg. It is classified as World Health Organization group 4 PH, and is the only type that can be surgically cured by pulmonary endarterectomy (PEA). This operation needs to be carried out by a team with strong expertise, from the diagnostic and decisional pathway to the operation itself. However, because the disease has a very heterogeneous phenotype in terms of anatomy, degree of PH and the lack of a standard patient profile, not all cases of CTEPH can be treated by PEA. As a result, PH-directed medical therapy traditionally used for the other types of PH has been proposed and is utilized in CTEPH patients. Since 2015, we have been witnessing the rebirth of balloon pulmonary angioplasty, a technique first performed in 2001 but has since fallen out fashion due to major complications. The refinement of such techniques has allowed its safe utilization as a salvage therapy in inoperable patients. In the present keynote lecture, we will describe these therapeutic approaches and results

Effects of diet on the outcomes of rheumatic and musculoskeletal diseases (RMDs): systematic review and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs

BackgroundA EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). In this paper, the literature on the effect of diet on the progression of RMDs is reviewed.MethodsSystematic reviews and meta-analyses were performed of studies related to diet and disease outcomes in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis, psoriatic arthritis, systemic sclerosis and gout. In the first phase, existing relevant systematic reviews and meta-analyses, published from 2013 to 2018, were identified. In the second phase, the review was expanded to include published original studies on diet in RMDs, with no restriction on publication date. Systematic reviews or original studies were included if they assessed a dietary exposure in one of the above RMDs, and reported results regarding progression of disease (eg, pain, function, joint damage).ResultsIn total, 24 systematic reviews and 150 original articles were included. Many dietary exposures have been studied (n=83), although the majority of studies addressed people with OA and RA. Most dietary exposures were assessed by relatively few studies. Exposures that have been assessed by multiple, well conducted studies (eg, OA: vitamin D, chondroitin, glucosamine; RA: omega-3) were classified as moderate evidence of small effects on disease progression.ConclusionThe current literature suggests that there is moderate evidence for a small benefit for certain dietary components. High-level evidence of clinically meaningful effect sizes from individual dietary exposures on outcomes in RMDs is missing

Paediatric recurrent pericarditis: Appropriateness of the standard of care and response to IL1-blockade

Objective: To analyse, in a cohort of paediatric patients with recurrent pericarditis (RP) undergoing anti-IL-1 treatment: the agent and dosing used as first line treatment, the long-term efficacy of IL1-blockers, the percentage of patients achieving a drug-free remission, the presence of variables associated with drug-free remission. Study design: Data were collected from patients' charts. Annualized relapse rate (ARR) was used for evaluation of treatment efficacy, bivariate logistic regression analysis for variables associated with drug-free remisison. Results: 58 patients, treated between 2008 and 2018, were included in the study (mean follow-up 2.6 years). 14/56 patients non-responsive to first line drugs were under-dosed. 57 patients were treated with anakinra: the ARR before and during daily treatment was 3.05 and 0.28, respectively (p<0.0001); an increase to 0.83 was observed after the reduction/withdrawal of treatment (p<.0001). The switch from anakinra to canakinumab (5 patients) was associated to an increase of the ARR (0.49 vs 1.46), but without statistical significance (p=0.215). At last follow-up only 9/58 patients had withdrawn all treatments. With the limits of a retrospective study and the heterogeneity between the patients enrolled in the study, a shorter duration of treatment with anakinra was the only variable associated with drug-free remission. Conclusion: This study shows that most of the pediatric patients with RP needing IL-1 blockade received an inadequate treatment with first line agents. The effectiveness of anakinra is supported by this study, but few patients achieved drug free-remission. The different rate of response to anakinra and canakinumab may suggest a possible role of IL1α in the pathogenesis of RP