Adult-Onset Still's Disease: A Case Report and Review of Current Therapeutic Options.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease that typically presents with a triad of fever, evanescent rash, and arthritis. There is often a delay in diagnosis of AOSD due to its nonspecific clinical presentation, which may mimic other infectious, rheumatological disorders, and malignancies. Corticosteroids have been the cornerstone for the management of AOSD for the past many years. However, with the expanding understanding of its pathogenesis, novel therapeutic options targeting various cytokines are being increasingly recognized. Herein, we present a case of AOSD that was successfully treated with tocilizumab, a monoclonal antibody against the interleukin-6 (IL-6) receptor. For the purpose of this article, we also conducted a literature search to review the current therapeutic options available for the treatment of AOSD.

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab.

INTRODUCTION: Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes. CASE REPORT: We present a rare case of an elderly male on pembrolizumab who suffered from four autoimmune toxicities including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica likely catalyzed by age-related immune activation.Management and outcome: Immunotherapy was indefinitely stopped, and patient was started on steroids for the immune-related adverse events with complete resolution of polymyalgia rheumatica. Thyroid dysfunction resolved once he started thyroid replacement therapy. His diabetes is well controlled with insulin and is followed by endocrinology. He continues on prednisone for immune-mediated pneumonitis with a good response with regular monitoring via computed tomography scans and pulmonary consultation. DISCUSSION: Few cases wherein multiple toxicities are seen within one patient are reported. Aging appears to be a risk factor for immune-related adverse events. Aging is associated with an increased incidence of autoimmunity as programmed death-1 ligand expression represents an important mechanism that tissues use to protect from self-reactive effector T cells. Programmed death-1 blockade breaks this protective mechanism and enhances autoimmune diseases. Therefore, close monitoring and extreme vigilance is warranted while using immune checkpoint inhibitors including pembrolizumab as multiple toxicities can occur within a short span of infusion, especially in elderly individuals. Prompt discontinuation and the use of a multidisciplinary team are prudent to prevent further morbidity and mortality.

Behcet's-like syndrome following pembrolizumab: An immune-related adverse event associated with programmed death receptor-1 inhibitor therapy.

INTRODUCTION: The landscape for the treatment of metastatic melanoma has been revolutionized with the introduction immune checkpoint inhibitors. Immune checkpoint inhibitors have now become the standard of care for the treatment of cancers. These immune agents including programmed death receptor-1 inhibitors, programmed death-ligand 1 inhibitors and cytotoxic T-lymphocyte antigen-4 inhibitors have shown promising results but have been associated with numerous immune-related complications. Pembrolizumab, a programmed death receptor-1 inhibitor, has been associated with a number of immune-related adverse events affecting multiple organ systems including integument, ocular, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, and musculoskeletal system. CASE REPORT: We present a case of an 88-year-old Caucasian male with metastatic melanoma of the face with metastasis to the right fifth cranial nerve and into the right cavernous sinus. He underwent resection of the melanoma and was placed on pembrolizumab at 2 mg/kg every three weeks. Interestingly, 24 months on pembrolizumab therapy, he developed corneal erosions, oral and genital ulcerations. MANAGEMENT AND OUTCOME: Patient completed his 24 months of pembrolizumab and was started on prednisone and colchicine with improvement in his symptoms. At his follow-up eight months, he had recurrence of an oral ulcer. DISCUSSION: Here we present a rare case of an elderly male on pembrolizumab who suffered from corneal erosions, oral and genital ulcers, a syndrome similar to Behcet's disease. Given that pembrolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the wide range immune-related adverse events including the possible Behcet's-like syndrome presentation.

Tuning of nanoparticle biological functionality through controlled surface chemistry and characterisation at the bioconjugated nanoparticle surface.

We have used a silica - PEG based bionanoconjugate synthetic scheme to study the subtle connection between cell receptor specific recognition and architecture of surface functionalization chemistry. Extensive physicochemical characterization of the grafted architecture is capable of capturing significant levels of detail of both the linker and grafted organization, allowing for improved reproducibility and ultimately insight into biological functionality. Our data suggest that scaffold details, propagating PEG layer architecture effects, determine not only the rate of uptake of conjugated nanoparticles into cells but also, more significantly, the specificity of pathways via which uptake occurs.

Diverse tumor pathology due to distinctive patterns of JAK/STAT pathway activation caused by different Drosophila polyhomeotic alleles.

Drosophila polyhomeotic (ph) is one of the important polycomb group genes that is linked to human cancer. In the mosaic eye imaginal discs, while ph(del), a null allele, causes only non-autonomous overgrowth, ph(505), a hypomorphic allele, causes both autonomous and non-autonomous overgrowth. These allele-specific phenotypes stem from the different sensitivities of ph mutant cells to the Upd homologs that they secrete.