Increased expression of long non-coding RNA FIRRE promotes hepatocellular carcinoma by HuR-CyclinD1 axis signaling.

There is a critical need to understand the disease processes and identify improved therapeutic strategies for hepatocellular carcinoma (HCC). The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. The aim of this study was to identify a lncRNA as a potential biomarker of HCC and investigate the mechanisms by which the lncRNA promotes HCC progression using human cell lines and in vivo. Using RNA-Seq analysis, we found that lncRNA FIRRE was significantly upregulated in hepatitis C virus (HCV) associated liver tissue and identified that lncRNA FIRRE is significantly upregulated in HCV-associated HCC compared to adjacent non-tumor liver tissue. Further, we observed that FIRRE is significantly upregulated in HCC specimens with other etiologies, suggesting this lncRNA has the potential to serve as an additional biomarker for HCC. Overexpression of FIRRE in hepatocytes induced cell proliferation, colony formation, and xenograft tumor formation as compared to vector-transfected control cells. Using RNA pull-down proteomics, we identified HuR as an interacting partner of FIRRE. We further showed that the FIRRE-HuR axis regulates cyclin D1 expression. Our mechanistic investigation uncovered that FIRRE is associated with an RNA-binding protein HuR for enhancing hepatocyte growth. Together, these findings provide molecular insights into the role of FIRRE in HCC progression.

Spontaneous development of myasthenia gravis and myositis following treatment with pembrolizumab: a case report.

BACKGROUND: Immune checkpoint inhibitors are a relatively new advancement in the world of cancer therapy. As such, their adverse effects have yet to be fully understood, with only recent literature documenting autoimmune phenomena secondary to their utilization. Specific immune checkpoint inhibitors have recently been linked with the development of myasthenia gravis, which is classically known to manifest spontaneously in patients. Given the relative rarity of this presentation, the risk of misdiagnosis and subsequent mortality and morbidity is concerning. CASE PRESENTATION: We discuss the case of a 73-year-old male who presented with clinical symptoms of myasthenia gravis and myositis shortly after beginning treatment with Pembrolizumab. The diagnosis of myasthenia gravis was initially missed at an outside hospital, which delayed initiation of proper treatment. CONCLUSION: While the incidence of "de-novo" diseases secondary to immune checkpoint inhibitors might be increasing, guidelines regarding best treatment options do not yet exist, leaving many providers at a loss when faced with making clinical decisions surrounding patients with De novo myasthenia gravis. Thus, our goal is to underscore the importance of early recognition of this disease, and emphasize the need for a standard of care as immune checkpoint inhibitors usage becomes more prevalent.

The Importance of Primary Care Cognitive Evaluation in Detecting an Atypical Presentation of Normal Pressure Hydrocephalus.

Normal pressure hydrocephalus (NPH) is a syndrome that characteristically presents with progressive gait impairment, cognitive deficits, and urinary urgency or incontinence. We present a case of a 54-year-old male with a past medical history of alcohol use and no primary care provider with new-onset auditory hallucinations. The patient was found to have a marked enlargement of the supratentorial and infratentorial ventricles on both computed tomography (CT) and magnetic resonance imaging (MRI) and an opening pressure of 21 on the lumbar puncture, concerning for NPH. Clinically, there were signs of cognitive impairment due to memory and cognitive function loss, but the patient lacked gait disturbances or incontinence. Although not common, NPH may present with auditory hallucinations or delusions, as seen with our patient. In this case report, we emphasize the importance of annual cognitive assessments in order to evaluate atypical psychiatric manifestations of neurological disorders. Because clinical symptoms are more likely to be reversible when recognized early in the clinical course and the progression of these symptoms can be prevented with the placement of a ventriculoperitoneal (VP) shunt, it is of utmost importance to accurately recognize and diagnose NPH as early as possible. We also discuss the less commonly known markers of NPH on MRI.

Neuro-Behçet's Syndrome Without Genital Ulcers: A Case Report and Literature Review.

Behçet's disease is a rare multisystemic vasculitis characterized by oral ulcers, genital ulcers, and skin and ocular lesions. Neuro-Behçet's syndrome is a condition in which individuals with Behçet's disease experience neurological symptoms that cannot be attributed to other neurological diseases. We present a rare case of neuro-Behçet's syndrome with acute internuclear ophthalmoplegia and deteriorating neurological function with a prior history of recurrent oral ulcers with pathergy-like features, acneiform papulopustular rash, retinal hemorrhages, and recurrent epididymitis without genital ulcers. Patient improved with cyclophosphamide. This case underscores the importance of diagnosing and managing neuro-Behçet's syndrome in the absence of genital ulcers.

Unprovoked Atypical Absence Status Epilepticus in a Patient With Allogeneic Stem Cell Transplantation.

Absence status epilepticus (ASE) is a rare but treatable condition, and when present in older adults, it can be misinterpreted as encephalopathy or behavioral changes. Our case discusses a 63-year-old patient with myelofibrosis and allogeneic stem cell transplant with late-onset de novo status epilepticus. This case report adds to the rare body of literature discussing de novo ASE whose clinical presentation can be indistinguishable from other encephalopathic or behavioral conditions. Moreover, its occurrence during oncologic treatment warrants clinicians to be on the lookout for similar presentations and encourages future reports of this condition in association with similar therapies. This case report provides value to providers treating patients with similar oncologic therapies and highlights the need for ASE to be further studied as it is a possible rare complication of allogeneic transplantation of stem cells.