S100 protein is a protein that has been considered to be specific for tissues of neuroectodermal origin; however, recent studies have demonstrated the presence of S100 protein in mesodermal tissues. Using immunohistochemical methods, we found S100 protein in human chordomas and in human and rabbit notochordal tissue. Our findings suggest that S100 protein is present not only in neuroectodermal tissue but in mesodermal tissue, which develops in close proximity to neuroectoderm.

S100 protein in human chordoma and human and rabbit notochord.

Archives of Pathology & Laboratory Medicine

Infarction (MINOCA) and ischaemia (INOCA) with non-obstructive coronary disease are recent non-conventional presentations of coronary syndromes that are increasingly recognised in the clinical arena, particularly with the availability of new cardiovascular imaging techniques. Both are related to heart failure (HF). MINOCA is not associated with benign outcomes, and HF is among the most prevalent events. Regarding INOCA, microvascular dysfunction has also been found to associate with HF, particularly with preserved ejection fraction (HFpEF).

Regardless of the several aetiologies underlying HF in MINOCA, it is likely related to LV dysfunction, where secondary prevention is not yet clearly established. Regarding INOCA, coronary microvascular ischaemia has been associated to endothelial dysfunction leading ultimately to diastolic dysfunction and HFpEF. MINOCA and INOCA are clearly related to HF. In both, there is a lack of studies on the identification of the risk factors for HF, diagnostic workup and, importantly, the appropriate primary and secondary prevention strategies.

MINOCA and INOCA: Role in Heart Failure.

Current Heart Failure Reports

Carvedilol, probably the β-blocker of choice for everyone with cirrhosis and portal hypertension: But not so fast!

Liver International : Official Journal of the International Association for the Study of the Liver

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody&#xa0;(ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Current practice relies on recommendations and guidelines addressing the management of ANCA-associated vasculitis and not specifically developed for EGPA. Here, we present evidence-based, cross-discipline guidelines for the diagnosis and management of EGPA that reflect the substantial advances that have been made in the past few years in understanding the pathogenesis, clinical subphenotypes and differential diagnosis of the disease, as well as the availability of new treatment options. Developed by a panel of European experts on the basis of literature reviews and, where appropriate, expert opinion, the 16 statements and five overarching principles cover the diagnosis and staging, treatment, outcome and follow-up of EGPA. These recommendations are primarily intended to be used by healthcare professionals, pharmaceutical industries and drug regulatory authorities, to guide clinical practice and decision-making in EGPA. These guidelines are not intended to limit access to medications by healthcare agencies, nor to impose a fixed order on medication use.

Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis.

Nature Reviews. Rheumatology

The management of acute ischemic stroke has undergone a paradigm shift in the past decade. This has been spearheaded by the emergence of endovascular thrombectomy, along with advances in medical therapy, imaging, and other facets of stroke care. Herein, we present an updated review of the various stroke trials that have impacted and continue to transform stroke management. It is critical for the radiologist to stay abreast of the ongoing developments to provide meaningful input and remain a useful part of the stroke team.

Advances in Acute Ischemic Stroke Treatment: Current Status and Future Directions.

AJNR. American Journal of Neuroradiology

Heart failure (HF) is a complex clinical syndrome involving structural and/or functional abnormalities of the heart. Heart failure is often classified based on left ventricular ejection fraction, which serves as a predictor of mortality. The majority of the data supporting disease-modifying pharmacological therapies are from patients with reduced ejection fraction (less than 40%). However, with the recent results from the sodium glucose cotransporter-2 inhibitor trials, there is renewed interest in identifying potential beneficial pharmacological therapies. This review focuses on and includes pharmacological HF therapies across the spectrum of ejection fraction, providing an overview of the novel trials. We also examined the effects of the treatments on mortality, hospitalization, functional status, and biomarker levels to further investigate the interplay between ejection fraction and HF.

Practical Pharmacological Treatment of Heart Failure: Does Ejection Fraction Matter Anymore?

Journal of Cardiovascular Development and Disease

Glomerulonephritis (GN) is a diverse group of immune-mediated disorders. Currently, GN is classified largely by histological patterns that are difficult to understand and teach and most importantly, do not indicate treatment choices. Indeed, altered systemic immunity is the primary pathogenic process and the key therapeutic target in GN. Here, we apply a conceptual framework of immune-mediated disorders to GN guided by immunopathogenesis and hence immunophenotyping: 1) Infection-related GN require pathogen identification and control, 2) Autoimmunity-related GN, defined by presence of autoantibodies, and 3) Alloimmunity-related GN in transplant recipients both require the suppression of adaptive immunity in lymphoid organs and bone marrow, 4) Autoinflammation-related GN, e.g. inborn errors of immunity diagnosed by genetic testing, requires suppression of single cytokine or complement pathways, and 5) Monoclonal gammopathy-related GN requires B or plasma cell clone-directed therapy. A new GN classification should include a) disease category, b) immunological activity to tailor the use of the increasing number of immunomodulatory drugs, and c) chronicity to trigger standard CKD care including the evolving spectrum of cardio-renoprotective drugs. Certain biomarkers allow diagnosis and the assessment of immunological activity and disease chronicity without kidney biopsy. These five GN categories and a therapy-focused GN classification is likely to overcome some of the existing hurdles in GN research, management, and teaching by reflecting disease pathogenesis and guiding the therapeutic approach.

The five types of glomerulonephritis classified by pathogenesis, activity, and chronicity (GN-AC).

Nephrology, Dialysis, Transplantation

Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults.

The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations.

The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone.

This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

S100 protein in human chordoma and human and rabbit notochord.

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