Immune checkpoint inhibitor-induced rheumatoid arthritis: insights into an increasingly common aetiology of polyarthritis

Nivolumab is an immune checkpoint inhibitor that is used in the treatment of a variety of cancers in the adjuvant or metastatic setting. Adverse effects include non-specific activation of T cells, leading to immune-related adverse events in downstream organs. We present a case of a 36-year-old man with unresectable oropharyngeal squamous cell carcinoma who developed nivolumab-induced rheumatoid arthritis. As immune checkpoint inhibitor use is becoming widespread in the medical oncology domain, the purpose of this case report is to increase awareness of an increasingly common cause of rheumatic disease and to alert clinicians to consider immunotherapy in their differential diagnosis of polyarthritis. This case also highlights the importance of working in an interdisciplinary manner to enhance cancer care for the patient as well as to increase awareness of the potential adverse effects of immunotherapy in patients with cancer.

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Effect of autologous adipose-derived mesenchymal stem cell therapy in the treatment of acromioclavicular joint osteoarthritis

The aim of this case report is to evaluate the efficacy of mesenchymal stem cell (MSC) therapy in the treatment of small joint osteoarthritis (OA). Acromio-clavicular (AC) joint OA is an under-diagnosed and yet frequent source of shoulder pain. MSCs have shown evidence of benefit in the treatment of knee OA. This is the first report to describe the use of MSC therapy in OA of the upper limb. A 43-year-old patient presents with painful AC joint OA and undergoes MSC therapy. The patient reported pain and functional improvement as assessed by the Disability of Arm, Shoulder and Hand Score and Numeric Pain Rating Scale. Imaging at 12 months showed structural improvement with reduction in subchondral oedema, synovitis and subchondral cysts. This case is the first to show the benefit of MSC therapy in the treatment of small joint arthropathy and also of the upper limb.

Trial registration number: Australian New Zealand Clinical Trials Registry (ACTRN12617000638336).

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Unexplained paraparesis following subarachnoid haemorrhage

Spinal arachnoid cysts (SAC) are rare in isolation and the exact aetiology is still debated. Primary (congenital) cysts are caused by structural abnormalities in the arachnoid layer and largely affect the thoracic region. Secondary cysts are induced by a multitude of factors, infection, trauma or iatrogenic response, and can affect any level of the spinal cord. While subarachnoid haemorrhage (SAH) is a relatively common condition with significant repercussions, it is extremely uncommonly associated with SAC. When present, it may develop in the months and years after the original bleed, giving rise to new neurological symptoms. Prompt treatment is needed to halt or reverse the worsening of symptoms and questions are still being asked about how best to approach this condition. A 42-year-old man presented with chronic back pain, severe worsening ataxia and numbness below the umbilicus, 7 months after treatment for a World Federation of Neurosurgical Societies grade five (WFNS V) SAH. Imaging revealed a SAC extending from T12 to L4 and causing thecal compression. This was treated with a L3 laminectomy andmarsupialisation. An improvement in neurological function was observed at 6 months. Aetiology of the SAC and its association with SAH are discussed and a review of the relevant literature is provided.

https://ift.tt/2VpvosU

Treatment-induced changes of lymphocyte subsets in patients with adenoid cystic carcinoma of the head and neck

Abstract

Purpose

Adenoid cystic carcinoma (ACC) of the head and neck is a rare and highly malignant tumor, characterized by perineural growth and early distant metastases. The composition of immune cells in the peripheral blood and the tumor microenvironment is critical to tumor growth and control. However, little is known about the frequency and function of the relevant immune cell subsets in this entity.

Methods

In ACC patients (n = 11) and matched healthy donors (n = 11), the frequency of peripheral blood T and B cells was measured by flow cytometry at different treatment stages of disease (24 samples). Cells were further characterized by their expression of CCR7, PD-1, CD39 and CD73. Tumor-infiltrating lymphocytes (TIL) were analyzed by immunohistochemistry for ten patients and for three patients by flow cytometry.

Results

CD4⁺ T cells had significantly lower frequency after radiotherapy (RT). All other cell frequencies, including T_reg, were stable through course of the disease. In B cells, CD73 was reduced after RT. CCR7 expression on T and B cells in patients with relapse/metastases (R/M) differed significantly from patients with active disease. PD-1 remained stable. T_reg were more present in TIL compared to peripheral blood.

Conclusion

Composition of lymphocyte subgroups behaves similar to squamous cell carcinoma in the head and neck, except for T_reg, which remained stable. Nevertheless, the CD4⁺/T_reg ratio was lower after RT, which could stand for an immunosuppressive effect in these patients. Therefore, it could be beneficial treating ACC with combined RT and immunomodulatory drugs.

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Structural Analysis of Recent Allergen-Antibody Complexes and Future Directions

Abstract

Purpose of Review

Allergen-antibody complexes are extremely valuable in describing the detailed molecular features of epitopes. This review summarizes insights gained from recently published co-structures and what obstacles impede the acquisition of further data.

Recent Findings

Structural epitope data helped define the epitopes of two anti-Fel d 1 antibodies undergoing phase I clinical trials, providing a greater level of detail than was possible through hydrogen-deuterium exchange protection studies. Separately, a human camelid-like antibody structure with lysozyme described several unique features in a long variable loop that interacted with the active site cleft of Gal d 4. Finally, a co-structure conclusively demonstrated that Phl p 7 could function as a superantigen and that an antibody could simultaneously recognize two epitopes. These remarkable assertions would not have been possible without visualization of the complex. Only three new complexes have appeared in the last few years, suggesting that there are major impediments to traditional production and crystallization.

Summary

The structural data was extremely valuable in describing epitopes. New techniques like cryo-EM may provide an alternative to crystallography.

https://ift.tt/2BQw5nN

Emerging Therapeutics for Ocular Surface Disease

Abstract

Purpose of Review

The purpose of this article is to review treatment advances in ocular allergy that include the treatment of the various signs and symptoms of the allergic inflammatory response of the ocular surface.

Recent Findings

Recent studies have demonstrated improved pharmacological effect of topical agents with artificial tears and cold compresses; brimonidine, a new ophthalmic decongestant which has demonstrated decreased rebound conjunctivitis; and potential use of contact lens and other novel delivery instruments to increase medication retention time.

Summary

Currently, there have been limited advances in novel ophthalmic treatments. Non-pharmacological interventions have demonstrated in a randomized control study that artificial tears and the use cold compresses alone or in combination with ophthalmic antihistamines can enhance the effectiveness of a traditional pharmacological therapy. The primary advances have been the start of head-to-head studies comparing various agents actively being used in the treatment of ocular allergy. In addition, there has been increasing interest in the development of novel delivery systems to increase residence time of pharmacological agents in the ocular surface such as nanoparticles, microfilms; examining novel pathways of controlling the allergic inflammatory response of the ocular surface such as modulation of cytokines, transcription factors, and immunophilins.

https://ift.tt/2UajuD2

New and Potential Treatments for Atopic Dermatitis: Biologicals and Small Molecules

Abstract

Purpose of Review

An update on new therapies currently approved or potentially useful in the future for the management of patients suffering moderate-to-severe atopic dermatitis.

Recent Findings

New pathogenic mechanisms involved in atopic dermatitis have permitted to propose novel therapeutic approaches devised to control the inflammatory process observed in involved cutaneous tissues by neutralizing mediators, cytokines, and their receptors.

Summary

Recent research findings have disclosed important and previously unrecognized pathogenic mechanisms that have resulted in innovative targeted therapies, such as dupilumab, and potentially other biologicals and small molecules. Further studies should permit the sub-classification of patients according to the relevance of different mediators and inflammatory cells. It can be concluded that the treatment of atopic dermatitis has entered into the era of personalized/precision medicine.

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