The story of dexamethasone and how it became one of the most widely used drugs in neurosurgery.

Dexamethasone, a long-acting potent glucocorticoid, is one of the most widely used medications in neurosurgery. In this paper, the authors recount the history of dexamethasone's rise in neurosurgery and discuss its use in brain tumors in the context of emerging neuro-oncological immunotherapies. In 1958, Glen E. Arth synthesized a 16-alpha-methylated analog of cortisone (dexamethasone) for treatment of rheumatoid arthritis. Joseph Galicich, a neurosurgery resident at the time, applied the rheumatological drug to neurosurgery. He gave doses to patients who had undergone craniotomy for tumor removal and saw their paresis improve, midline shift resolve, and mortality rates decrease. He advocated for clinical trials and the drug became a mainstay in neurosurgery. As neuro-oncological treatments evolve to include immunotherapy, the immunosuppressive effects of dexamethasone are becoming an unwanted effect. The question then becomes: how does one treat the patient's symptoms if the only drug that has been used throughout history may become a detriment to their oncological treatment? Since its discovery, dexamethasone has maintained an impressive staying power in the field, acting as a standard drug for cerebral edema for more than 60 years. However, with the advent of immunotherapy, research is warranted to evaluate ways of treating symptomatic edema in the context of modern neuro-oncological therapies.

Propensity score methods in the surgical oncology literature.

The use of propensity score methods in the surgical literature is increasing. Randomized, controlled clinical trials are the gold standard of medical research, allowing for accurate measurement and analysis of treatment effects. Use of propensity score methods allows researchers to mimic randomization when true randomization may not be possible. When used properly, these methods are a powerful tool for the medical researcher, allowing more rigorous conclusions to be drawn from retrospective data. With the increasing prevalence of propensity methods, it is important that these methods are used correctly, lest researchers be led to misleading conclusions based on poor statistical study design and analysis. The objective of this review is to analyze and evaluate the use of propensity score methods in the surgical oncology literature. We critique the current state of the use of propensity scores in the surgical oncology literature and offer recommendations to assure appropriate usage of propensity score methods.

Charles Jacques Bouchard (1837-1915) and the Charcot-Bouchard aneurysm.

Charles Jacques Bouchard was a distinguished French physician and scientist of the early 19th century. Despite his humble beginnings, Bouchard was able to achieve meteoric success within the scientific and medical fields, establishing himself as one of the most influential physician-scientists of his time. This was in part due to his superb commitment, as well as the prosperity engendered by the strong influence of his teachers, which can be seen as a testament to the importance of mentorship in medicine. Besides his myriad contributions, Bouchard is most well known for describing the Charcot-Bouchard aneurysm in 1866 alongside his mentor Jean-Martin Charcot, linking them for the first time to intracranial hemorrhage. Bouchard's thesis entitled "A Study of Some Points in the Pathology of Cerebral Hemorrhage" was regarded by some as the most original and important of all recent works on the subject of cerebral hemorrhage at the time of publication. Sadly, the great relationship Bouchard shared with his mentor Charcot would later deteriorate into perhaps one of the most well-known student-mentor quarrels in the history of medicine. Herein, the authors present a historical recollection of Bouchard's life, career, and contributions to medicine, as well as the famous controversy with Jean-Martin Charcot.

Leptomeningeal disease in glioblastoma: endgame or opportunity?

INTRODUCTION: Glioblastoma is an aggressive cancer with a notoriously poor prognosis. Recent advances in treatment have increased overall survival, though this may be accompanied by an increased incidence of leptomeningeal disease (LMD). LMD carries a particularly severe prognosis and remains a late stage manifestation of glioblastoma without satisfactory treatment. The objective of this review is to survey the literature on treatment of LMD in glioblastoma and to more fully characterize the current therapeutic strategies. METHODS: The authors performed a systematic review following PRISMA criteria on PubMed and OVID databases. Articles that included adult patients with LMD from glioblastoma were retrieved and reviewed. RESULTS: LMD in glioblastoma patients is increasing in incidence, with reports of up to 21%. The overall survival without treatment is alarmingly brief, with patients surviving between 1.6-3.8 months. All studies showed that treatment does improve overall survival significantly, increasing to 11.7 months in one study. However, no one adjuvant or surgical therapy has been shown to improve survival in LMD significantly over another. Direct treatment methods include chemotherapy (standard, anti-angiogenic, intrathecal, immunotherapy), and radiation. Hydrocephalus is a complication in LMD that can be treated with ventriculoperitoneal shunt placement, however treating hydrocephalus and delivering intrathecal chemotherapy is a challenge. CONCLUSION: Though evidence remains lacking and there is no consensus, treatments show a trend towards improving survival and should be considered on a case-by-case basis. Further studies are necessary in the pursuit of a standard of care.

Relapse risk factors for patients with comorbid affective disorders and substance abuse disorders from an intensive treatment unit.

BACKGROUND AND OBJECTIVES: The prevalence of substance use disorders (SUD), particularly involving opiates and benzodiazepines, has increased to the detriment of public health and the economy. Here, we evaluate relapse factors among the high-risk demographic of patients with SUD and comorbid affective disorders. METHODS: A retrospective chart review of 76 patients discharged after detoxification and simultaneous psychiatric care for concomitant affective disorders and SUDs. Relapse was assessed by two independent evaluators via postdischarge chart review, which included state-wide healthcare utilization, by patient, through healthcare information exchange systems. A Cox Hazards analysis was performed to characterize relapse risk factors. RESULTS: Benzodiazepine use, admission through the emergency department (ED) rather than direct admission, frequent ED use in the preceding year, and history of prior attendance at multiple detoxification programs were risk factors for shortened time-to-relapse. Polysubstance use and intravenous drug use prolonged time to relapse. DISCUSSION AND CONCLUSIONS: Notable findings include the significant relapse risk associated with benzodiazepine abuse and frequent prior ED utilization. These risk factors could reflect a number of underlying mediators for relapse, including anxiety, disease burden, and malingering. Additionally, this study recapitulates the observation in other patient populations that the majority of health resource utilization is attributed to a small population of patients. SCIENTIFIC SIGNIFICANCE: This study is the first to identify relapse predictors among dual-diagnosis affective disorder and SUD patients in survival analysis, and replicates the alarming and largely unknown effect that benzodiazepines have on increasing relapse risk.