Secukinumab versus guselkumab in the complete resolution of ustekinumab-resistant psoriatic plaques: The ARROW study.

Interleukin (IL)-23-independent IL-17A production has been suggested to be involved in persistent manifestations of psoriatic disease, including anti-IL-12/23-refractory psoriatic plaques; this study aimed to test this hypothesis by investigating the clinical and molecular effects of direct IL-17A (with secukinumab) versus selective IL-23 inhibition (with guselkumab) in patients with anti-IL-12/23 (ustekinumab)-refractory psoriatic plaques. A 16-week, randomized, open-label, parallel-group, Phase IIa study (ARROW, NCT03553823) was conducted in patients with ≥1 active psoriatic plaque (total clinical score [TCS] ≥6) at screening despite treatment with ustekinumab, and a Psoriasis Area and Severity Index (PASI) score 1-10. Patients were randomized 1:1 to receive secukinumab 300 mg (n = 20) or guselkumab 100 mg (n = 20).

Management of heart failure with reduced ejection fraction in Europe: design of the ARIADNE registry.

Aims: The introduction of sacubitril/valsartan (an angiotensin receptor-neprilysin inhibitor) is likely to change the approach to the management of patients with chronic heart failure with reduced ejection fraction (HFrEF). The Assessment of Real Life Care-Describing European Heart Failure Management (ARIADNE) registry will evaluate patient characteristics, practice patterns, outcomes, and healthcare resource utilization in the outpatient setting across Europe, with the main focus on factors that guide physicians' decisions to start and continue sacubitril/valsartan in patients with HFrEF.

Methods And Results: ARIADNE, a prospective, observational registry will enrol 9000 ambulatory patients with HFrEF in 23 European countries Supplement 1.

Selective up-regulation of the soluble pattern-recognition receptor pentraxin 3 and of vascular endothelial growth factor in giant cell arteritis: relevance for recent optic nerve ischemia.

Objective: To assess local expression and plasma levels of pentraxin 3 (PTX3) in patients with giant cell arteritis (GCA).

Methods: Plasma and serum samples were obtained from 75 patients with GCA (20 of whom had experienced optic nerve ischemia in the previous 3 weeks and 24 of whom had experienced symptom onset in the previous 6 months and had no history of optic nerve ischemia) and 63 controls (35 age-matched healthy subjects, 15 patients with rheumatoid arthritis, and 13 patients with chronic stable angina). In 9 patients in whom GCA was recently diagnosed, circulating levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p70, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1α (MIP-1α), CCL4/MIP-1β, CCL11/eotaxin, CXCL9/monokine induced by interferon-γ, CXCL10/interferon-γ-inducible 10-kd protein, tumor necrosis factor α (TNFα), interferon-γ, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor, and FasL were measured via a multiplexed cytometric assay.

Chromogranin A: a novel factor acting at the cross road between the neuroendocrine and the cardiovascular systems.

Chromogranin A (CHGA) is a secretory protein stored in and released from neurons and cells of the diffuse neuroendocrine system. Cells of the adrenal medulla and adrenergic terminals are a main source of CHGA but also myocardial cells produce it under stress conditions. After secretion, CHGA is cleaved into several biologically active fragments, including vasostatins and catestatin.

Phase I study of non-pegylated liposomal doxorubicin in combination with ifosfamide in adult patients with metastatic soft tissue sarcomas.

Objective: The aim of this study was to evaluate the maximum tolerated dose (MTD) and safety of the combination of non- pegylated liposomal doxorubicin (Myocet) and ifosfamide in patients with metastatic soft tissue sarcomas.

Methods: Cohorts of four patients with metastatic soft tissue sarcomas received up to five cycles of intravenous ifosfamide 3000 mg/m2 on days 1- 3 in combination with escalating doses of intravenous Myocet on day 1 every 3 weeks until dose limiting toxicity (DLT) in at least one patient. Starting dose of Myocet was 40 mg/m2 to be escalated through 10 mg/m2 increase up to 80 mg/m2.

The clinical spectrum of the neurological involvement in vasculitides.

Both the central nervous system (CNS) and the peripheral nervous system (PNS) are major target organs in primary vasculitides. They may either be affected in the setting of systemic vasculitis, potentially involving any other organ, or they may be the sole site of the inflammatory process. In both cases, the clinical pattern of PNS involvement is essentially uniform, presenting as sensory axonal polyneuropathy or mononeuritis multiplex.

Circulating chromogranin A reveals extra-articular involvement in patients with rheumatoid arthritis and curbs TNF-alpha-elicited endothelial activation.

TNF-alpha plays an important role in the natural history of rheumatoid arthritis (RA), a systemic disease characterized by endothelial activation and synovial involvement with bone erosions. Neuroendocrine signals contribute as well to RA, but their role is poorly understood. We measured in 104 RA patients and in an equal number of sex- and age-matched, healthy controls the blood levels of chromogranin A (CgA), a candidate marker linking the neuroendocrine system to TNF-alpha-mediated vascular inflammation.

Conversation galante: how the immune and the neuroendocrine systems talk to each other.

The generation of endogenous adjuvants and the clearance of apoptotic cells occur at the intersection between the neuroendocrine and the immune systems. Recent data suggest that autoimmunity associates with a communication breakdown between the two systems and that events taking place in lymphoid organs and in peripheral inflamed tissues shape the response to tissue damage. Autonomic nerve endings release norepinephrine and acetylcholine, whereas sensitive fibers release neuropeptides.

Neuroendocrine modulation induced by selective blockade of TNF-alpha in rheumatoid arthritis.

Tumor necrosis factor-alpha (TNFalpha) is a main actor in the pathogenesis of rheumatoid arthritis (RA), interacting with other molecules in complex mechanisms. The neuroendocrine system is known to be involved and Chromogranin A (CHGA) serum levels are elevated in patients with RA. We evaluated the effect of the selective blockade of TNF-alpha, induced by treatment with anti-TNF-alpha monoclonal antibodies (mAbs), on the serum levels of CHGA and on its correlation with TNF-alpha and TNF-alpha receptors (TNFRs) serum levels.

Hypoglycaemia and lactic acidosis in a MALT non Hodgkin's lymphoma.

Hypoglycaemia associated with lactic acidosis is a rare complication of lymphomas; only four cases have been previously reported. Recent studies provide evidence of direct consumption of glucose by the tumour cells, leading to lactic acidosis. We report the case of a 64-year-old patient with a gastric diffuse large B cell non-Hodgkin's lymphoma transformed from an indolent mucosa associated lymphoid tissue (MALT) lymphoma, admitted to our department for acute renal failure due to a tumour lysis syndrome.