Selected Domains within a Comprehensive Geriatric Assessment in Older Patients with Non-Hodgkin Lymphoma are Highly Associated with Frailty.

Background: The incidence of Non-Hodgkin Lymphoma (NHL) is increasing, particularly among older patients who tend to have worse outcomes and can be predisposed to increased toxicities and less treatment tolerance. Therefore, a thorough pre-treatment assessment is essential. A comprehensive geriatric assessment (CGA) can be used to evaluate the older patient considering chemotherapy and is the preferred evaluation tool.

Outcomes using direct-acting antiviral hepatitis-C treatment in older versus younger Veterans.

Background: Historically, older adults have been excluded from trials evaluating hepatitis C virus (HCV) treatment, in part, due to the adverse effects associated with previous regimens. Veterans are at high risk of HCV infection. Ledipasvir/sofosbuvir (LED/SOF) is a once daily antiviral regimen with demonstrated efficacy and tolerability among the younger population.

Therapeutic Advances for Pancreatic Cancer: a Slow and Challenging Feat that Continues to Evolve.

Despite precision medicine and advances in oncology such as immunotherapy and targeted therapy that have made substantial strides in certain solid malignancies, effective treatment options are still needed for pancreatic cancer, a highly-lethal disease with a dismal prognosis. Current treatment regimens with antimetabolites and taxanes have only modestly improved survival rates, and surgery remains the only curative measure, with just a minority of patients being eligible for curative surgery at the time of diagnosis. The role of traditional anti-cancer approaches such as radiation has yet to be definitively determined for this malignancy, and more contemporary approaches such as targeted therapy are limited in pancreatic cancer.

The Role of the Comprehensive Geriatric Assessment in the Evaluation of the Older Cancer Patient.

Geriatric assessments have now been recommended as part of the standard evaluation of an older adult considering cancer therapy. While the need for a more in-depth performance status evaluation of an older person with cancer was identified over 20 years ago, completion of a comprehensive geriatric assessment (CGA) is time-consuming and not frequently performed as part of the standard assessment of older cancer patients. Evidence suggests that incorporating such an evaluation could be useful for potentially determining the patient's chemotherapy tolerability or treatment completion, toxicity, and survival, as age alone has been shown to poorly predict treatment failure, and performance status assessments commonly used in oncology practice may lack predictability.

A Severe Episode of Hemolytic Anemia After Amoxicillin Exposure in A G6PD Deficient Patient.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide, with genetic variants resulting in a range of phenotypes that vary from asymptomatic to severe hemolysis. We report a case of severe hemolytic anemia in a G6PD deficient patient whose only known exposure was amoxicillin two weeks prior to his episode of severe hemolysis, for which he presented to our hospital. An extensive infectious and hematologic workup resulted negative with the exception of a positive G6PD deficiency result.

An Uncommon Cause of Dysphagia in a 35 Year Old Male.

Typical causes of intermittent esophageal dysphagia in a young person include eosinophilic esophagitis, esophageal dysmotility and esophageal rings. We report a 35-year-old male with a one year history of intermittent dysphagia to solid foods. After the endoscopic removal of a food bolus, a barium swallow revealed extrinsic compression of the proximal esophagus.

UPFRONT DPD DEFICIENCY DETECTION TO SECURE 5-FU ADMINISTRATION: PART 2- APPLICATION TO HEAD-AND-NECK CANCER PATIENTS.

Background: Upfront screening for dihydropyrimidine dehydrogenase (DPD) deficiency in patients scheduled for 5-FU should help reduce the risk of toxicities by preventive adaptive dosing. Our group has developed a simple functional testing categorizing patients upon their DPD status, i.e.

A long journey to short abbreviations: developing an open-source framework for clinical abbreviation recognition and disambiguation (CARD).

Objective: The goal of this study was to develop a practical framework for recognizing and disambiguating clinical abbreviations, thereby improving current clinical natural language processing (NLP) systems' capability to handle abbreviations in clinical narratives.

Methods: We developed an open-source framework for clinical abbreviation recognition and disambiguation (CARD) that leverages our previously developed methods, including: (1) machine learning based approaches to recognize abbreviations from a clinical corpus, (2) clustering-based semiautomated methods to generate possible senses of abbreviations, and (3) profile-based word sense disambiguation methods for clinical abbreviations. We applied CARD to clinical corpora from Vanderbilt University Medical Center (VUMC) and generated 2 comprehensive sense inventories for abbreviations in discharge summaries and clinic visit notes.

A genome-wide association study of heparin-induced thrombocytopenia using an electronic medical record.

Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect of heparin treatment resulting from an immune response to platelet factor 4 (PF4)/heparin complexes. No genome-wide evaluations have been performed to identify potential genetic influences on HIT. Here, we performed a genome-wide association study (GWAS) and candidate gene study using HIT cases and controls identified using electronic medical records (EMRs) coupled to a DNA biobank and attempted to replicate GWAS associations in an independent cohort.

Oxidative stress modulates PPAR gamma in vascular endothelial cells.

The peroxisome proliferator-activated receptor gamma (PPAR gamma) plays an important role in vascular regulation. However, the impact of oxidative stress on PPAR gamma expression and activity has not been clearly defined. Human umbilical vein endothelial cells (HUVECs) were exposed to graded concentrations of H(2)O(2) for 0.

Thiazolidinediones as anti-cancer agents.

The PPAR-gamma (PPAR-γ) activating thiazolidinedione (TZD) medications are a class of drugs used to improve lipid and glucose metabolism in type-2 diabetes. In addition to their known insulin sensitization action, these drugs have been shown to suppress tumor development in several in vitro and in vivo models. Among the proposed mechanisms for the anti-tumor effects of TZDs, apoptosis induction, cell cycle arrest, and differentiation have been extensively reported.

Attenuation of signaling and nitric oxide production following prolonged leptin exposure in human aortic endothelial cells.

Acute leptin exposure stimulates endothelial nitric oxide (NO) production in vitro. In contrast, chronic elevations in circulating leptin levels in patients with obesity are associated with endothelial dysfunction and impaired endothelial NO production. Therefore, the goal of the current study was to examine the direct effects of acute and more sustained leptin stimulation on endothelial nitric oxide synthase (eNOS) and NO production in human aortic endothelial cells (HAECs).

Suppression of thymidine phosphorylase expression by promoter methylation in human cancer cells lacking enzyme activity.

Purpose: Thymidine phosphorylase (TP, EC 2.4.2.

A rapid and inexpensive method for anticipating severe toxicity to fluorouracil and fluorouracil-based chemotherapy.

Dihydropyrimidine dehydrogenase (DPD) deficiency leads to dramatic overexposure to fluorouracil (5-FU), resulting in a potentially lethal outcome in patients treated with standard doses. The aim of this study was to validate, in a routine clinical setting, a simple and rapid method to determine the DPD status in a subset of cancer patients, all presenting with life-threatening toxicities following 5-FU or capecitabine intake. In this study, 80 out of 615 patients (13%) suffered severe toxicities, including 5 lethal ones (0.

Multiple gene expression analyses in paraffin-embedded tissues by TaqMan low-density array: Application to hedgehog and Wnt pathway analysis in ovarian endometrioid adenocarcinoma.

Recent studies have shown the hedgehog and Wnt families of signaling proteins to be associated with tumor initiation, growth, and survival. However, these pathways remain unexplored in ovarian endometrioid adenocarcinoma (OEA). Here, we describe a novel TaqMan low-density array to examine the expression of 26 and 20 genes in the hedgehog and Wnt pathways, respectively, in six matched snap-frozen and formalin-fixed, paraffin-embedded (FPE) OEA specimens.

Antitumor efficacy of capecitabine and celecoxib in irradiated and lead-shielded, contralateral human BxPC-3 pancreatic cancer xenografts: clinical implications of abscopal effects.

Purpose: X-ray therapy (XRT) remains one of the major modalities used to treat patients diagnosed with locally advanced pancreatic adenocarcinoma. However, the effect of XRT on metastatic tumors outside the field of irradiation (abscopal effect) remains largely unknown. In the current study, we examined the effect of XRT alone and in combination with capecitabine and/or celecoxib in both irradiated and lead-shielded contralateral BxPC-3 pancreatic cancer xenografts.

Increased peptidylarginine deiminase type II in hypoxic astrocytes.

Peptidylarginine deiminase type II (PAD 2) is the primary enzyme responsible for conversion of protein bound arginine to citrulline in the central nervous system. Evidence suggests that glial fibrillary acidic protein (GFAP), the main intermediate filament in astrocytes, is deiminated, but not much is known regarding factors that control this enzymatic reaction. The present study demonstrated that PAD 2 activity (as determined by Western blot analysis of citrullinated GFAP isoforms) was increased in human cultured astrocytes by hypoxic conditions.

Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation.

In the United States, tumors of the central nervous system remain the third leading cancer-related cause of death in young adults with a median survival time of < 1 year. A recent case study suggested that Capecitabine (a novel, fluoropyrimidine prodrug) may be effective in the treatment of brain metastases. Pharmacogenomic studies have correlated the antitumor response to Capecitabine with the expression of the drug metabolizing enzymes thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD).