Glioblastoma multiforme (GBM), which is the most common primary central nervous system malignancy in adults, has long presented a formidable challenge to researchers and clinicians alike. Dismal ...5-year survival rates of the patients with these tumors and the ability of the recurrent tumors to evade primary treatment strategies have prompted a need for alternative therapies in the treatment of GBM. Histone deacetylase (HDAC) inhibitors are currently a potential epigenetic therapy modality under investigation for use in GBM with mixed results. While these agents show promise through a variety of proposed mechanisms in the pre-clinical realm, only several of these agents have shown this same promise when translated into the clinical arena, either as monotherapy or for use in combination regimens. This review will examine the current state of use of HDAC inhibitors in GBM, the mechanistic rationale for use of HDAC inhibitors in GBM, and then examine an exciting new mechanistic revelation of certain HDAC inhibitors that promote antitumor immunity in GBM. The details of this antitumor immunity will be discussed with an emphasis on application of this antitumor immunity towards developing alternative therapies for treatment of GBM. The final section of this article will provide an overview of the current state of immunotherapy targeted specifically to GBM.
Individuals having sustained traumatic spinal cord injury (TSCI) in the United States are living longer as compared to historical trends, thanks to an ever-evolving understanding of the nature of ...this injury. Despite this, multiple barriers to care for TSCI patients remain including variations in government-issued veteran insurance, privatized insurance, and among uninsured individuals. The United States alone experiences 12,000 new TSCI cases every year, many of these are found to occur in a growing proportion of elderly individuals. It is crucial to understand both the short-term direct costs as wells as the long-term rehabilitation costs required by these TSCI patients. The lifetime financial burden for those having sustained a TSCI can be immense for patients, insurance companies, and hospital systems alike. Among those with TSCI, re-hospitalization rates are high, leading to increased healthcare resource utilization within this specific patient population. Costs can quickly balloon into hundreds of thousands of dollars and cause a profound financial burden for these patients. This review article seeks to communicate an understanding of the current financial landscape surrounding TSCI patients. The authors will also examine the costs of acute emergency room surgical care such as American spinal injury association grade, hospital length of stay, as well as the timing delay between injury and surgical decompression. Long-term costs associated with TSCI such as rehabilitation, care of secondary comorbidities, and post-injury employment prospects will be examined as well. These costs will be framed from the patient's perspective as well as from both the hospital and insurance company's perspectives. It is hoped a complete understanding as to what makes TSCI such a medically and financially burdensome injury will allow for improved healthcare resource utilization in this population.
Lipoprotein lipase (LPL) has emerged as a distinct prognostic marker for chronic lymphocytic leukemia (CLL), a heterogeneous disease with a similar heterogeneity in life expectancy. While many prior ...studies have focused on tumor expression of LPL mRNA, LPL surface protein expression has been less robustly studied as a prognostic marker. A novel antibody developed at Geisel School of Medicine at Dartmouth has been previously utilized in immunohistochemistry assays of breast and prostate cancer. With this study we aimed to use this antibody as a flow cytometry marker of surface LPL expression correlated with overall survival and time to first treatment. Of the 19 patients studied, our data show that LPL surface protein expression as measured by flow cytometry trended toward a protective effect on overall survival and overall better prognosis.
Diagnostic codes are crucial for analyses of electronic health record (EHR) data but their accuracy and precision are often lacking. Although providers enter precise diagnoses into progress notes, ...billing standards may limit the particularity of a diagnostic code. Variability also arises from the creation of multiple descriptions for a particular diagnostic code. We hypothesized that the variability of diagnostic codes would be greater before surgical pathology results were recorded in the medical record. A well annotated cohort of patients with brain neoplasms was studied. After diagnostic pathology reporting, the odds of more distinct diagnostic descriptions were 2.30 times higher (p=0.00358), entropy in diagnostic sequences was 2.26 times higher (p=0.0259) and entropy in diagnostic precision scores was 15.5 times higher (p=0.0324). Although diagnostic codes became more distinct on average after diagnostic pathology reporting, there was a paradoxical increase in the variability of the codes selected. Researchers must be aware of the inconsistencies and variability in particularity in structured diagnostic coding despite the presence of a definitive diagnosis.
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