Thymoma and Myasthenia Gravis: An Examination of a Paraneoplastic Manifestation.

Thymoma is a rare type of malignancy but is considered one of the most common neoplasms that occur in the anterior mediastinum. A large proportion of thymomas are associated with paraneoplastic syndromes, such as myasthenia gravis. Whenever feasible, the standard of care for the treatment of thymoma should focus on the control of paraneoplastic syndromes, surgical resection, and adjuvant therapy if appropriate. A 36-year-old female patient with a significant past medical history of obesity and iron deficiency anemia who underwenten bloc resection of thymoma three months prior now presented to the benign hematology clinic to establish care for the management of anemia. Upon review of systems, the patient incidentally reported fatigue, weakness with repetitive motion, occasional blurred vision, headaches, and exertional dyspnea. Physical examination was positive for horizontal nystagmus. Given the patient's history and clinical findings, suspicion of myasthenia gravis was high. Further work-up demonstrated anti-acetylcholine receptor titers of 5.70 nmol/L (normal < 0.21 nmol/L), supporting a diagnosis of myasthenia gravis in this patient. She was subsequently started on pyridostigmine. Often, patients with thymoma experience paraneoplastic syndrome-related symptoms prior to thymectomy, and in many cases thymectomy is curative. However, in the case presented, we examine a patient that was asymptomatic prior to surgery and subsequently reported the onset of symptoms following what we suspect was an exacerbation due to general anesthesia and pain control medications. We argue that all patients with thymoma should undergo systematic evaluation and treatment of paraneoplastic syndromes, regardless of clinical symptoms and prior to surgery, in order to improve patient quality of life and hospital outcomes.

High-Sensitivity C-Reactive Protein and Magnetic Resonance Imaging in Occult Giant Cell Arteritis.

Giant cell arteritis (GCA) can be an elusive diagnosis and is particularly challenging to monitor during the course of treatment when traditional acute phase reactants are all normal, leaving no empirical means of monitoring. Our study aims to explore the use of more sensitive acute phase reactants and imaging in the initial evaluation and monitoring of GCA. We report the case of an 84-year-old in whom the traditional acute phase reactants were normal but who had perineuritis on imaging and whose high-sensitivity C-reactive protein (CRP) levels were elevated. In cases where the traditional measure of inflammatory activity is normal, it may be necessary to consider additional markers.

Review of Cognitive Biases in ACGME Milestones Training Assessments in Post-graduate Medical Education Programs.

The course of study for young physicians for post-graduate training is an exciting and life-changing opportunity, one that is filled with the relentless optimism of intellectual discovery and personal growth and development. The American Council for Graduate Medical Education (ACGME) is a non-profit private council that evaluates and accredits internship, residency, and fellowship programs. The role of the ACGME is to oversee curriculums, training environments, and specialty evaluation standards to ensure satisfactory competency leading to board eligibility and certification in the respected field of study. The ACGME has the monumental task of guiding educational standards that are designed to both protect the public welfare and further educational programs. Many educational standards are objective, such as quantitative performance on examinations, involvement in research, and involvement in systems development and quality improvement. However, key clinical performance measures are based on prior training and experience. Over the last several years, studies examining rates of abuse and discrimination during post-graduate medical training in both the United States and Canadian studies, which have reported alarmingly high rates of 50%. With the increasing utility and availability of social media, such issues have become more transparent to the public. A plethora of studies has been conducted, examining physician biases towards patients, practice changes, insurance company regulations, and evolving healthcare systems. However, a significant amount of evaluation is merited when examining individual institutional cultures and the educational environments that harbor them. We wish to examine the role of ever-evolving specialty-specific ACGME-instituted educational milestones in Internal Medicine and Opthalmology in the context of potential cognitive biases and their implementation within post-graduate training programs.

Integration of Next-generation Sequencing and Immune Checkpoint Inhibitors in Targeted Symptom Control and Palliative Care in Solid Tumor Malignancies: A Multidisciplinary Clinician Perspective.

The molecular characterization of solid tumor malignancies with respect to tumorgenesis, risk stratification, and prognostication of chemotherapeutic side effects is multi-faceted. Characterizing these mechanisms requires a detailed understanding of cytogenetics and pharmacology. In addition to the standard palliative care interventions that address issues such as fatigue, neuropathy, performance status, depression, nutrition, cachexia, anxiety, and medical ethics, we must also delve into individual chemotherapy side effects. Comprehending these symptoms is more complex with the advent of broader targeted therapies. With the advent and initiation of Foundation Medicine (FMI) testing, we have been able to tailor regimens to the individual genetics of the patient. Next-generation sequencing (NGS) is a bioinformatic analysis used in order to create a targeted effort to understand the complex genetics of a vast array of malignancies. Through the process known as high-throughput sequencing we, as clinicians, can obtain more real-time genetic data and incorporate the information into our reasoning process. The process involves a broad manner in which deoxyribonucleic acid (DNA) sequence data is obtained including genome sequencing and resequencing, protein-DNA or proteinomics, chromatin immunoprecipitation (ChIP)-sequencing, ribonucleic acid (RNA) sequencing, and epigenomic analysis. High-throughput sequencing techniques including single molecule real-time sequencing, ion semiconductor sequencing, pyrose sequencing, sequencing by synthesis, sequencing by ligation, nanopore sequencing, and chain termination (otherwise known as Sanger sequencing) have expanded the realm of NGS and clinicians options.

Evaluation, Identification, and Management of Acute Methotrexate Toxicity in High-dose Methotrexate Administration in Hematologic Malignancies.

The pharmacological and medical management of complex chemotherapy regimens are vast and complex, requiring an intimate understanding of physiology, particularly when novel biologic agents are utilized with commonly used regimens. The molecular classification in patients with diffuse large B-cell lymphoma (DLBCL) is multifaceted, particularly with the expansion of novel molecular targets. The pharmacological and medical management of hematologic malignancies with a tendency to have central nervous system (CNS) involvement is complex and requires an understanding of physiology and pharmacology. Many chemotherapy regimens used to treat hematologic malignancies with either CNS involvement or high risk for CNS disease will include the administration of high dose methotrexate. This requires having physiological understanding with respect to the standard regimens for DLBCL in addition to understanding cytogenetic markers, such as c-myc and bcl-2, the expression of which displays increased likelihood of CNS involvement. In patients with documented CNS disease and active neurological manifestations such as myclonus, headaches, nystagmus, and blurred vision, the utilization of high dose methotrexate has become an essential standard of care. We examine the pharmacologic mechanisms of high dose methotrexate in patients with hematologic malignancies such as DLBCL and review the most common toxicities on a multidisciplinary level.

Polyparaneoplastic Manifestations of Malignant Thymoma: A Unique Case of Myasthenia, Autoimmune Hepatitis, Pure Red Cell Aplasia, and Keratoconjunctivitis Sicca.

Thymomas are relatively uncommon malignancies of the anterior mediastinum and present with four distinct histological types based on the specific epithelial to lymphocyte ratio: spindle cell, epithelial predominant, lymphocyte predominant, or mixed. Each histologic type of thymoma has a propensity for local invasion and metastasis and can have a wide variety of paraneoplastic manifestations, myasthenia being the most common. We present a unique case of a 34-year-old African-American female who initially presented with a history of profound weakness with repetitive motion, shortness of breath, horizontal nystagmus, persistent anemia, keratoconjunctivitis sicca, and what was initially thought to be azithromycin-induced hepatitis. Upon left anterior thoracotomy with biopsy of the mediastinal mass, pathology yielded a lymphocyte-predominant (B1), Masaoka stage IVA invasive thymoma with pericardial extension. This case illustrates the clinical significance of considering a multitude of extrathymic paraneoplastic manifestations, each with a unique physiological mechanism.

Biological agents for the treatment of uveitis.

INTRODUCTION: The conventional treatment of uveitis includes corticosteroids and immunosuppressive agents, which are highly efficacious, but can be associated with serious systemic side effects. Over the last two decades, advances in the understanding of the pathogenesis of inflammatory diseases, as well as improved biotechnology, have enabled selective targeting of the chemical mediators of diseases. Recently, a new class of drugs called biologics, that target the various mediators of the inflammation cascade, may potentially provide more effective and less toxic treatment. AREAS COVERED: This article is a review and summary of the peer-reviewed evidence for biologic agents in the treatment of various forms of ocular inflammation and it focuses on the potential use of other biologic agents that have been tested in experimental autoimmune uveitis. Pubmed was used as our main tool for our literature search. Some additional references were taken from books written on the subject. EXPERT OPINION: There are a wide variety of new and emerging biological agents currently being used in the treatment of uveitis which has expanded the therapeutic horizons far beyond previous limitations.

Superoxide is an associated signal for apoptosis in axonal injury.

Optic neuropathy is the leading cause of irreversible blindness, and a paradigm for central nervous system axonal disease. The primary event is damage to retinal ganglion cell axons, with subsequent death of the cell body by apoptosis. Trials of neuroprotection for these and other neuronal diseases have mostly failed, primarily because mechanisms of neuroprotection in animals do not necessarily translate to humans. We developed a methodology for imaging an intracellular transduction pathway that signals neuronal death in the living animal. Using longitudinal confocal scanning multilaser ophthalmoscopy, we identified the production of superoxide within retrograde-labelled rat retinal ganglion cells after optic nerve transection. Superoxide was visualized by real-time imaging of its reaction product with intravitreally administered hydroethidine and confirmed by differential spectroscopy of the specific product 2-hydroxyethidium. Retinal ganglion cell superoxide increased within 24 h after axotomy, peaking at 4 days, and was not observed in contralateral untransected eyes. The superoxide signal preceded phosphatidylserine externalization, indicating that superoxide generation was an early event and preceded apoptosis. Intravitreal pegylated superoxide dismutase blocked superoxide generation after axotomy and delayed retinal ganglion cell death. Together, these results are consistent with superoxide being an upstream signal for retinal ganglion cell apoptosis after optic nerve injury. Early detection of axonal injury with superoxide could serve as a predictive biomarker for patients with optic neuropathy.