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.
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.
The course of study for young physicians for postgraduate training is an exciting and lifechanging 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 postgraduate 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 everevolving specialty-specific ACGME-instituted educational milestones in Internal Medicine and Opthalmology in the context of potential cognitive biases and their implementation within postgraduate training programs.
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