scholarly journals Neutrophil Extracellular Trap-Driven Occlusive Diseases

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2208
Author(s):  
Kursat Oguz Yaykasli ◽  
Christine Schauer ◽  
Luis E. Muñoz ◽  
Aparna Mahajan ◽  
Jasmin Knopf ◽  
...  
Keyword(s):  
Stone Formation ◽  
Neutrophil Extracellular Trap ◽  
Treatment Modalities ◽  
Pancreatic Ducts ◽  
Tubular Structures ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
The Enlightenment ◽  
Life Threatening ◽  
Initial Idea

The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various diseases. The initial idea that NETs are a pivotal defense structure was gradually amended due to several deleterious effects in consecutive investigations. NETs formation is now considered a double-edged sword. The harmful effects are not limited to the induction of inflammation by NETs remnants but also include occlusions caused by aggregated NETs (aggNETs). The latter carries the risk of occluding tubular structures like vessels or ducts and appear to be associated with the pathologies of various diseases. In addition to life-threatening vascular clogging, other occlusions include painful stone formation in the biliary system, the kidneys, the prostate, and the appendix. AggNETs are also prone to occlude the ductal system of exocrine glands, as seen in ocular glands, salivary glands, and others. Last, but not least, they also clog the pancreatic ducts in a murine model of neutrophilia. In this regard, elucidating the mechanism of NETs-dependent occlusions is of crucial importance for the development of new therapeutic approaches. Therefore, the purpose of this review is to address the putative mechanisms of NETs-associated occlusions in the pathogenesis of disease, as well as prospective treatment modalities.

Fifty Years of Experience with Chordomas in Southeast Scotland

Neurosurgery ◽  
1985 ◽  
Vol 16 (2) ◽  
pp. 166-170 ◽  
Author(s):  
P. O'Neill ◽  
B.A. Bell ◽  
J.D. Miller ◽  
I. Jacobson ◽  
W. Guthrie
Keyword(s):  
Clinical Presentation ◽  
Surgical Intervention ◽  
Slow Growth ◽  
Multicenter Trial ◽  
Treatment Modalities ◽  
Therapeutic Approaches ◽  
Slow Growth Rate ◽  
The Past ◽  
New Therapeutic Approaches

Abstract We report the clinical presentation and management of 34 patients with a histologically proven chordoma, treated in the neurosurgical departments in Edinburgh and Dundee, over the past 50 years. Although these tumors are commonly regarded as being locally invasive with a variable, but generally slow growth rate, they can metastasize, and this may precede surgical intervention, as in one of our patients. Our cases are compared to those in previously published series, and a comprehensive review of the treatment modalities for tumors at various sites is presented. The optimal treatment to be recommended from our own experience, and that of others, is aggressive operation and radiotherapy. A combination of hyperthermia and chemotherapy has shown some promise, but remains untested, and highlights the need for a multicenter trial with long follow-up to allow the evaluation of new therapeutic approaches.

scholarly journals Approach to Hemoptysis in the Modern Era

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Sébastien Gagnon ◽  
Nicholas Quigley ◽  
Hervé Dutau ◽  
Antoine Delage ◽  
Marc Fortin
Keyword(s):  
Argon Plasma Coagulation ◽  
Argon Plasma ◽  
Regenerated Cellulose ◽  
Therapeutic Approaches ◽  
Antifibrinolytic Agents ◽  
Endoscopic Techniques ◽  
New Therapeutic Approaches ◽  
Life Threatening ◽  
Diagnostic Modalities ◽  
Modern Era

Hemoptysis is a frequent manifestation of a wide variety of diseases, with mild to life-threatening presentations. The diagnostic workup and the management of severe hemoptysis are often challenging. Advances in endoscopic techniques have led to different new therapeutic approaches. Cold saline, vasoconstrictive and antifibrinolytic agents, oxidized regenerated cellulose, biocompatible glue, laser photocoagulation, argon plasma coagulation, and endobronchial stents and valves are amongst the tools available to the bronchoscopist. In this article, we review the evidence regarding the definition, etiology, diagnostic modalities, and treatment of severe hemoptysis in the modern era with emphasis on bronchoscopic techniques.

scholarly journals Potent Killing of Pseudomonas aeruginosa by an Antibody-Antibiotic Conjugate

mBio ◽  
2021 ◽  
Author(s):  
Kimberly K. Kajihara ◽  
Homer Pantua ◽  
Hilda Hernandez-Barry ◽  
Meredith Hazen ◽  
Kiran Deshmukh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Clinical Success ◽  
Therapeutic Approaches ◽  
Preclinical Stage ◽  
Content Type ◽  
New Therapeutic Approaches ◽  
Life Threatening

Antibiotic treatment of life-threatening P. aeruginosa infections is associated with low clinical success, despite the availability of antibiotics that are active in standard microbiological in vitro assays, affirming the need for new therapeutic approaches. Antibiotics often fail in the preclinical stage due to insufficient efficacy against P. aeruginosa .

Poly(ADP-Ribose) Polymerase-1 Inhibitors Drug Discovery, Design, and Development as Anticancer Agents from Past to Present: A Mini-Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Arwa AlGhamdi ◽  
Hanine AlMubayedh
Keyword(s):  
Anticancer Agents ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Therapeutic Approaches ◽  
Repair Mechanism ◽  
Design And Development ◽  
Cancer Treatments ◽  
New Therapeutic Approaches ◽  
Life Threatening ◽  
Cancerous Cells

Abstract: Cancer treatments are known for their life-threatening toxicities attributed to their low selectivity; hence, new therapeutic approaches are being developed as alternatives. Among those approaches is the DNA repair mechanism, where its inhibition results selectively in the death of cancerous cells. Poly(ADP-Ribose) Polymerase (PARP) is one of the enzymes involved in the repair of damaged DNA. The inhibition of PARP shows to be a promising approach for effective targeted treatment of cancer, especially in tumours with pre-existing Homologous-Repair (HR) defects (i.e., BRCA). Nicotinamide, which is one of the PARP catalytic products, was the first identified PARP inhibitor (PARPi). The first FDA-approved PARPi was Olaparib in 2014 for the treatment of BRCA mutated advanced ovarian cancer. Several clinical trials have been conducted to further improve PARPi. However, there are some concerns related to drug resistance, PARPi sensitive-tumour identification, and toxic accumulation of PARPi. This report will review the uses of PARPi, drug design and development of PARPi from past to present, current issues, and prospective plans.

scholarly journals Current Opinion and Knowledge on Peritoneal Carcinomatosis: A Survey among a Swiss Oncology Network

Chemotherapy ◽  
2018 ◽  
Vol 63 (3) ◽  
pp. 143-147 ◽  
Author(s):  
Fabian Grass ◽  
David Martin ◽  
Michael Montemurro ◽  
Patrice Mathevet ◽  
Anita Wolfer ◽  
...  
Keyword(s):  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Modalities ◽  
Therapeutic Approaches ◽  
Current Opinion ◽  
New Therapeutic Approaches ◽  
Case Vignettes ◽  
Colorectal Origin ◽  
New Treatment ◽  
Practice Knowledge

Aims of the Study: The present survey aimed to evaluate current opinion and practice regarding peritoneal metastasis (PM), satisfaction with available treatment options, and need for new therapeutic approaches. Methods: This was a qualitative study conducted between October 2016 and October 2017 in the Réseau Suisse Romand d’Oncologie including 101 members of various oncological specialties. Participants’ demographics, current practice, knowledge, and satisfaction regarding available treatment options and need for new treatment options were assessed by semantic differential scales through 33 closed questions with automatic reminders at 4-, 8-, 12-, and 16-week intervals. Results: Twenty-seven participants (27%) completed the survey. Participants were gastrointestinal or gynecologic oncologists and surgeons. Most participants (67%) evaluated their knowledge on PM as moderate, while 22% considered themselves as experts. Clinical usefulness of systemic chemotherapy and hyperthermic intraperitoneal chemotherapy was judged to be moderate to high for PM of ovarian and colorectal origin and moderate to poor for gastric origin. Satisfaction with available treatment options was 6/10 (interquartile range [IQR] 4–7) for ovarian, 5/10 (IQR 3–7) for colorectal, and 3/10 (IQR 1–3) for gastric PM. Treatment strategies varied widely for typical case vignettes. The need for new treatment modalities was rated as 8/10 (IQR 6–10). Conclusion: Usefulness of and satisfaction with available treatment options for PM were rated as moderate at best by oncological experts, and treatment strategies differed importantly among participants. There appears to be a clear need for standardization and new treatment modalities.

scholarly journals Immunomodulation as a Therapy for Aspergillus Infection: Current Status and Future Perspectives

2018 ◽  
Vol 4 (4) ◽  
pp. 137 ◽  
Author(s):  
Chris Lauruschkat ◽  
Hermann Einsele ◽  
Juergen Loeffler
Keyword(s):  
Immune Cell ◽  
Current Knowledge ◽  
Antifungal Drugs ◽  
Current Status ◽  
Remission Induction ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Life Threatening ◽  
Broad Variety ◽  
Immunological Recovery

Invasive aspergillosis (IA) is the most serious life-threatening infectious complication of intensive remission induction chemotherapy and allogeneic stem cell transplantation in patients with a variety of hematological malignancies. Aspergillus fumigatus is the most commonly isolated species from cases of IA. Despite the various improvements that have been made with preventative strategies and the development of antifungal drugs, there is an urgent need for new therapeutic approaches that focus on strategies to boost the host’s immune response, since immunological recovery is recognized as being the major determinant of the outcome of IA. Here, we aim to summarize current knowledge about a broad variety of immunotherapeutic approaches against IA, including therapies based on the transfer of distinct immune cell populations, and the administration of cytokines and antibodies.

scholarly journals Dysregulated neutrophil responses and neutrophil extracellular trap formation and degradation in PAPA syndrome

2018 ◽  
Vol 77 (12) ◽  
pp. 1825-1833 ◽  
Author(s):  
Pragnesh Mistry ◽  
Carmelo Carmona-Rivera ◽  
Amanda K Ombrello ◽  
Patrycja Hoffmann ◽  
Nickie L Seto ◽  
...  
Keyword(s):  
Neutrophil Extracellular Trap ◽  
Therapeutic Approaches ◽  
Gene Signatures ◽  
New Therapeutic Approaches ◽  
Papa Syndrome ◽  
Healthy Control ◽  
Skin Biopsies ◽  
Neutrophil Infiltrate

ObjectivesPyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is characterised by flares of sterile arthritis with neutrophil infiltrate and the overproduction of interleukin (IL)-1β. The purpose of this study was to elucidate the potential role of neutrophil subsets and neutrophil extracellular traps (NET) in the pathogenesis of PAPA.MethodsNeutrophils and low-density granulocytes (LDG) were quantified by flow cytometry. Circulating NETs were measured by ELISA and PAPA serum was tested for the ability to degrade NETs. The capacity of NETs from PAPA neutrophils to activate macrophages was assessed. Skin biopsies were analysed for NETs and neutrophil gene signatures.ResultsCirculating LDGs are elevated in PAPA subjects. PAPA neutrophils and LDGs display enhanced NET formation compared with control neutrophils. PAPA sera exhibit impaired NET degradation and this is corrected with exogenous DNase1. Recombinant human IL-1β induces NET formation in PAPA neutrophils but not healthy control neutrophils. NET formation in healthy control neutrophils is induced by PAPA serum and this effect is inhibited by the IL-1 receptor antagonist, anakinra. NETs from PAPA neutrophils and LDGs stimulate IL-6 release in healthy control macrophages. NETs are detected in skin biopsies of patients with PAPA syndrome in association with increased tissue IL-1β, IL-8 and IL-17. Furthermore, LDG gene signatures are detected in PAPA skin.ConclusionsPAPA syndrome is characterised by an imbalance of NET formation and degradation that may enhance the half-life of these structures in vivo, promoting inflammation. Anakinra ameliorates NET formation in PAPA and this finding supports a role for IL-1 signalling in exacerbated neutrophil responses in this disease. The study also highlights other inflammatory pathways potentially pathogenic in PAPA, including IL-17 and IL-6, and these results may help guide new therapeutic approaches in this severe and often treatment-refractory condition.

New therapeutic approaches for polymyositis and dermatomyositis

2011 ◽  
Vol 152 (39) ◽  
pp. 1552-1559 ◽  
Author(s):  
Katalin Dankó ◽  
Melinda Vincze
Keyword(s):  
Immunosuppressive Agents ◽  
Inflammatory Myopathy ◽  
Proximal Muscle ◽  
Therapeutic Approaches ◽  
First Line ◽  
New Therapeutic Approaches ◽  
Remission Period ◽  
Immune Mediated ◽  
Systemic Manifestations ◽  
Line Of Therapy

Inflammatory myopathies are chronic, immune-mediated diseases characterized with progressive proximal muscle weakness. They encompass a variety of syndromes with protean manifestations. The aims of therapy are to increase muscle strength, prevent the development of contractures, and to manage the systemic manifestations of the disease. This is a complex treatment which requires routine and wide knowledge. The most important task is to recognize the disease and guide the patient to immunologic center. Although the first line of therapy continues to include corticosteroids, there are a multitude of agents available for treating patients with myositis. There are several different immunosuppressive agents which may be applied alone or in combination with each other, as well as an increasing number of novel and exciting biologic agents targeting molecules participating in the pathogenesis of inflammatory myopathy. Physiotherapy and rehabilitation in the remission period may significantly improve the functional outcome of patients with these disorders. Orv. Hetil., 2011, 152, 1552–1559.

Alteraciones sistémicas y metabólicas producidas por lesión medular

2019 ◽  
Vol 1 (1) ◽  
pp. 59-75
Author(s):  
Gabriel Guízar Sahagún
Keyword(s):  
Spinal Cord ◽  
Daily Living ◽  
Autonomic Function ◽  
Clinical Presentation ◽  
Scientific Literature ◽  
International Standards ◽  
Therapeutic Approaches ◽  
Cord Injury ◽  
Life Threatening ◽  
The Impact

Besides the well-known loss of motor and sensory capabilities, people with spinal cord injury (SCI) experience a broad range of systemic and metabolic abnormalities including, among others, dysfunction of cardiovascular, respiratory, gastrointestinal, urinary, and endocrine systems. These alterations are a significant challenge for patients with SCI because such disorders severely interfere with their daily living and can be potentially life-threatening. Most of these disorders are associated with impairment of regulation of the autonomic nervous system, arising from disruption of connections between higher brain centers and the spinal cord caudal to the injured zone. Thus, the higher and more complete the lesion, the greater the autonomic dysfunction and the severity of complications.This article summarizes the medical scientific literature on key systemic and metabolic alterations derived of SCI. It provides information primarily focused on the pathophysiology and clinical presentation of these disorders, as well as some guides to prevent and alleviate such complications. Due to the impact of these alterations, this topic must be a priority and diffuse to those involved with the care of people with SCI, including the patient himself/herself. We consider that any collaborative effort should be supported, like the development of international standards, to evaluate autonomic function after SCI, as well as the development of novel therapeutic approaches.

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