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Immunomodulatory therapy

Sarah E Nelson, Panayiotis N Varelas
PURPOSE OF REVIEW: Status epilepticus, refractory status epilepticus, and super-refractory status epilepticus can be life-threatening conditions. This article presents an overview of the three conditions and discusses their management and outcomes. RECENT FINDINGS: Status epilepticus was previously defined as lasting for 30 minutes or longer but now is more often defined as lasting 5 minutes or longer. A variety of potential causes exist for status epilepticus, refractory status epilepticus, and super-refractory status epilepticus, but all three ultimately involve changes at the cellular and molecular level...
December 2018: Continuum: Lifelong Learning in Neurology
Benjamin Mesure, Patrick Menu, Jagadeesh Kumar Venkatesan, Magali Cucchiarini, Émilie Velot
Musculoskeletal pathologies, especially those affecting bones and joints, remain a challenge for regenerative medicine. The main difficulties affecting bone tissue engineering are the size of the defects, the need for blood vessels and the synthesis of appropriate matrix elements in the engineered tissue. Indeed, the cartilage is an avascular tissue and consequently has limited regenerative abilities. Thanks to their self-renewal, plasticity and immunomodulatory properties, mesenchymal stem cells (MSCs) became a central player in tissue engineering, and have already been shown to be able to differentiate towards chondrogenic or osteogenic phenotypes...
December 5, 2018: Current Stem Cell Research & Therapy
J M Mor, K R Koch, V Kakkassery, C Cursiefen, L M Heindl
BACKGROUND: Benign iridal tumors rarely necessitate a therapeutic intervention. In contrast, malignant tumors of the iris can threaten the patient's life and eyesight and require early treatment to prevent the development of metastases. OBJECTIVE: Presentation of current treatment options for iridal tumors with special emphasis on iridal melanoma. METHODS: This article gives an overview of the current literature based on a PubMed search as well as own clinical experience...
December 4, 2018: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
Paul Lohan, Nick Murphy, Oliver Treacy, Kevin Lynch, Maurice Morcos, Bingling Chen, Aideen E Ryan, Matthew D Griffin, Thomas Ritter
High-risk cornea transplant recipients represent a patient population with significant un-met medical need for more effective therapies to prevent immunological graft rejection due to heightened anti-donor immune response. In this study, a rat model of pre-existing anti-donor immunity was developed in which corneal allografts were rejected earlier than in non-pre-sensitized recipients. In this model, third-party (non-donor, non-recipient strain) allogeneic mesenchymal stromal cells (allo-MSC) were administered intravenously 7 and 1 days prior to transplantation...
2018: Frontiers in Immunology
Serhat Emeksiz, Nurettin Onur Kutlu, Nuri Alaçakır, Hüseyin Çaksen
Emeksiz S, Kutlu NO, Alaçakır N, Çaksen H. A case of steroid-resistance Hashimoto's encephalopathy presenting with sensorimotor polyneuropathy. Turk J Pediatr 2018; 60: 310-314. Hashimoto`s encephalopathy (HE) is a rare, auto-immune disease characterized by symptoms of acute or subacute encephalopathy associated with increased anti-thyroid antibody levels. The course of most HE cases is relapsing and remitting, which is similar to that of vasculitis and stroke. Steroids are the first line treatment in HE...
2018: Turkish Journal of Pediatrics
Fatemeh Rezaei, Seyed Mohammad Moazzeni
Objective: Mesenchymal stem cells (MSCs), due to their immunomodulatory functions, are an ideal candidate for the treatment of immune-related diseases. Recurrent spontaneous abortion (RSA) is one of the most common complications of pregnancy which in many cases is related to the immune system disorders. Our previous study has shown that the abortion rate was decreased following the syngeneic MSCs therapy in abortion-prone mice. In this study, the therapeutic effect of syngeneic, allogeneic, and xenogeneic MSCs was compared in a mouse model of RSA...
April 2019: Cell Journal
Philippe Lavigne, Stella E Lee
Objective: To provide new insight into how chronic rhinosinusitis (CRS) is conceptualized and treated with a focus on immunomodulator therapy. Data sources: Pubmed, Medline, and Embase. Methods: A current review of the evidence is provided for immunomodulators investigated for treatment of CRS with nasal polyps (CRSwNP). Results: Biologic therapies targeting IgE, IL-4, IL-5, and IL-13 for the treatment of CRSwNP have shown promise and are currently in phase 3 trials...
September 2018: World Journal of Otorhinolaryngology—Head and Neck Surgery
Anna E Oja, Berber Piet, David van der Zwan, Hans Blaauwgeers, Mark Mensink, Sander de Kivit, Jannie Borst, Martijn A Nolte, René A W van Lier, Regina Stark, Pleun Hombrink
Resident memory T cells (TRM ) inhabit peripheral tissues and are critical for protection against localized infections. Recently, it has become evident that CD103+ TRM are not only important in combating secondary infections, but also for the elimination of tumor cells. In several solid cancers, intratumoral CD103+ CD8+ tumor infiltrating lymphocytes (TILs), with TRM properties, are a positive prognostic marker. To better understand the role of TRM in tumors, we performed a detailed characterization of CD8+ and CD4+ TIL phenotype and functional properties in non-small cell lung cancer (NSCLC)...
2018: Frontiers in Immunology
Bharat Bhushan, Vijay Sardana, Dilip Maheshwari, Piyush Ojha, Sankalp Mohan, Parag Moon, Sumit Kamble, Nishtha Jain, Sunil K Sharma
Introduction: Our aim was to study dengue-related immune-mediated neurological complications (IMNC) during the recent epidemic. Materials and Methods: This was a cross-sectional observational study of 79 IMNC cases from 1627 laboratory confirmed dengue cases from January 2015 to January 2016 and their follow-up for 3 months. According to the World Health Organization, cases were categorized into those having dengue fever (DF), and those having a severe syndrome that includes dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS)...
November 2018: Neurology India
Amy Klion
Hypereosinophilic syndromes (HESs) are a heterogeneous group of rare disorders characterized by peripheral eosinophilia and eosinophilic end organ complications. Conventional therapies, including glucocorticoids and cytotoxic and immunomodulatory agents, have variable efficacy and significant toxicity. Although the recent development of agents that target eosinophils, including tyrosine kinase inhibitors and monoclonal antibodies, provides the possibility of more effective, less toxic approaches to treatment of HES, there are little available data to guide their use in these conditions...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Elisabet E Manasanch, Jatin J Shah, Hans C Lee, Donna M Weber, Sheeba K Thomas, Behrang Amini, Lei Feng, Zuzana Berkova, Michelle Hildebrandt, Robert Z Orlowski
BACKGROUND: Bortezomib with lenalidomide and dexamethasone (VRd) is a standard regimen for the front-line treatment of multiple myeloma. Panobinostat is approved in combination with bortezomib and dexamethasone in patients with myeloma who 'have been given at least two previous regimens including bortezomib and an immunomodulatory agent. We aimed to determine the maximum tolerated dose of a new regimen combining VRd with panobinostat in patients with newly diagnosed multiple myeloma. METHODS: In this phase 1 study, we enrolled patients from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) with newly diagnosed multiple myeloma who were aged 18 years or older and eligible for autologous stem-cell transplant (ASCT) according to International Myeloma Working Group 2014 diagnostic criteria...
December 2018: Lancet Haematology
Pezhman Mobasher, Mehran Heydari Seradj, Jodie Raffi, Margit Juhasz, Natasha Atanaskova Mesinkovska
INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin disease. Conventional treatments include topical emollients, corticosteroids, calcineurin inhibitors, phototherapy, and systemic immunomodulatory agents, however, these medications have limitations in the treatment of moderate to severe AD. Current literature demonstrates that oral small molecules may be an effective modality to treat AD. METHOD: Using PubMed/MEDLINE, Embase, Cochrane Skin databases and clinicaltrials...
December 2, 2018: Journal of Dermatological Treatment
Ivonne Hernandez Schulman, Wayne Balkan, Joshua M Hare
Chronic diseases and degenerative conditions are strongly linked with the geriatric syndrome of frailty and account for a disproportionate percentage of the health care budget. Frailty increases the risk of falls, hospitalization, institutionalization, disability, and death. By definition, frailty syndrome is characterized by declines in lean body mass, strength, endurance, balance, gait speed, activity and energy levels, and organ physiologic reserve. Collectively, these changes lead to the loss of homeostasis and capability to withstand stressors and resulting vulnerabilities...
2018: Frontiers in Nutrition
Maiko Matsushita, Mai Kawaguchi
Recent advances in cancer immunotherapy, including immune checkpoint inhibitors or adoptive T cell therapies, have contributed to better outcomes in cancer patients. However, there are still many cancers with no cure. Therefore, combinations of several treatment strategies are being explored, and enhancing anticancer immunity will play an important role to combat the disease. There have been several reports on the immune-modulatory effects of commonly used drugs, namely, statin, metformin, and angiotensin receptor blockers (ARBs), which suggest that these drugs could enhance immunity against cancer cells...
2018: Journal of Oncology
Patrick Baah Ampomah, Wan Ting Kong, Olga Zharkova, Sonja C J H Chua, R Perumal Samy, Lina H K Lim
Influenza A viruses (IAVs) are important human respiratory pathogens which cause seasonal or periodic endemic infections. IAV can result in severe or fatal clinical complications including pneumonia and respiratory distress syndrome. Treatment of IAV infections is complicated because the virus can evade host immunity through antigenic drifts and antigenic shifts, to establish infections making new treatment options desirable. Annexins (ANXs) are a family of calcium and phospholipid binding proteins with immunomodulatory roles in viral infections, lung injury, and inflammation...
2018: Frontiers in Pharmacology
Daniel H Whittam, Emma C Tallantyre, Stephen Jolles, Saif Huda, Robert J Moots, Ho Jin Kim, Neil P Robertson, Bruce A C Cree, Anu Jacob
Rituximab is a widely used B-cell-depleting monoclonal antibody. It is unlicensed for use in neurological disorders and there are no treatment guidelines. However, as a rapidly acting, targeted therapy with growing evidence of efficacy and tolerability in several neuroinflammatory disorders, it is an attractive alternative to conventional immunomodulatory medications. This practical review aims to explain the basic principles of B-cell depletion with therapeutic monoclonal antibodies. We present the evidence for using rituximab in neurological diseases, and describe the practical aspects of prescribing, including dosing, monitoring, safety, treatment failure and its use in special circumstances such as coexisting viral hepatitis, pregnancy and lactation...
November 29, 2018: Practical Neurology
Candy S Hwang, Beverly Ellis, Bin Zhou, Kim D Janda
Heroin is a highly abused opioid that has reached epidemic status within the United States. Yet, existing therapies to treat addiction are inadequate and frequently result into rates of high recidivism. Vaccination against heroin offers a promising alternative therapeutic option but requires further development to enhance the vaccine's performance. Hsp70 is a conserved protein with known immunomodulatory properties and is considered an excellent immunodominant antigen. Within an antidrug vaccine context, we envisioned Hsp70 as a potential dual carrier-adjuvant, wherein immunogenicity would be increased by co-localization of adjuvant and antigenic drug hapten...
November 20, 2018: Bioorganic & Medicinal Chemistry
Anna Wrona
PURPOSE OF REVIEW: Despite aggressive treatment based on definitive chemoradiotherapy, 5-year overall survival in unresectable stage III nonsmall cell lung cancer remains poor (15-20%). The novel immunotherapy based on immune checkpoint inhibitors (ICIs) presents as the therapeutic 'Holly Grail' in lung cancer treatment. RECENT FINDINGS: Preclinical models provide evidence of immunotherapy-radiotherapy (IM-RT) synergy. The exposure to ionizing radiation turns tumor in an in-situ vaccine, primes the innate immune system, increases immunotherapy efficacy by overcoming the immunosuppressive microenvironment of immune-resistant tumors and promotes a systemic, out-of-field antitumor T-cell-mediated response called abscopal effect...
January 2019: Current Opinion in Oncology
Suraj P Parihar, Reto Guler, Frank Brombacher
Statins were first identified over 40 years ago as lipid-lowering drugs and have been remarkably effective in treating cardiovascular diseases. As research advanced, the protective effects of statins were additionally attributed to their anti-inflammatory, antioxidative, anti-thrombotic and immunomodulatory functions rather than lipid-lowering abilities alone. By promoting host defence mechanisms and inhibiting pathological inflammation, statins increase survival in human infectious diseases. At the cellular level, statins inhibit the intermediates of the host mevalonate pathway, thus compromising the immune evasion strategies of pathogens and their survival...
November 28, 2018: Nature Reviews. Immunology
Javed Mahmood, Hem D Shukla, Sandrine Soman, Santanu Samanta, Prerna Singh, Shriya Kamlapurkar, Ali Saeed, Neha P Amin, Zeljko Vujaskovic
Pancreatic cancer (PC) has the highest mortality rate amongst all other cancers in both men and women, with a one-year relative survival rate of 20%, and a five-year relative survival rate of 8% for all stages of PC combined. The Whipple procedure, or pancreaticoduodenectomy, can increase survival for patients with resectable PC, however, less than 20% of patients are candidates for surgery at time of presentation. Most of the patients are diagnosed with advanced PC, often with regional and distant metastasis...
November 28, 2018: Cancers
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