The Impact of Non-opioid Analgesic Usage on Total Opioid Load During Traumatic Brain Injury Rehabilitation: A Retrospective Study.

Background Patients staying in acute rehabilitation often use large amounts of opioids during their stay. There are a number of reasons for this increased opioid exposure, including but not limited to daily exercises with physical and occupational therapists, increased demand on a healing body, and use of previously atrophying musculature. Some physiatrists have noticed that patients who concurrently are prescribed medications such as Robaxin seem to require fewer opioids during their stay in acute rehabilitation. This study aimed to determine the association between non-opioid analgesic use and total opioid load, as measured using morphine milligram equivalents (MMEs), during inpatient rehabilitation for traumatic brain injury. Methodology A retrospective study of individuals with a diagnosis of traumatic brain injury admitted to an acute inpatient rehabilitation program was performed. Non-opioid medications that were reviewed in the study included acetaminophen, amitriptyline, baclofen, diclofenac, gabapentin, ibuprofen, lidocaine, methocarbamol, nortriptyline, and pregabalin. Five of the most-used non-opioid medications (acetaminophen, diclofenac, gabapentin, lidocaine, and methocarbamol) were statistically analyzed using regression and analysis of variance to evaluate for any significant variables. Results Results showed that the average daily dose of acetaminophen has a significant effect on the average daily MME and that the average daily dose of gabapentin and methocarbamol each have a significant effect on the change of daily MME usage from admission to discharge from acute rehab (ΔMME). Results also showed that the mere presence of methocarbamol (regardless of daily or total dosage) had a significant effect on the ΔMME. Conclusions Based on these findings, physicians may want to consider prescribing acetaminophen, gabapentin, or methocarbamol for patients admitted for inpatient rehabilitation following traumatic brain injury who require high amounts of opioids.

Association Between Height and Clinical Outcome in Metastatic Colorectal Cancer Patients Enrolled Onto a Randomized Phase 3 Clinical Trial: Data From the FIRE-3 Study.

BACKGROUND: Previous studies have found significant relationships between height and colorectal cancer (CRC) risk. Increased growth has been associated with activated pathways such as insulin-like growth factor 1. This study examined the impact of height on outcomes in metastatic CRC patients enrolled onto the FIRE-3 study, a randomized phase 3 clinical trial. PATIENTS AND METHODS: A total of 695 patients with metastatic CRC were studied and height was measured in centimeters. Male patients were grouped as ≤ 165, 166-175, 176-185, and ≥ 186 cm in height; female patients were grouped as ≤ 154, 155-164, 165-174, and ≥ 175 cm in height. Primary end point was overall survival (OS); secondary end point was progression-free survival. RESULTS: When patients' heights were categorized into 4 groups, the tallest group showed a worse OS compared to the shortest group; however, there was no linear relationship between height and OS. To investigate this, we showed the association between height as a continuous variable and OS. Patients shorter than 172 cm had a worse OS as their height decreased. Patients taller than 172 cm had a worse OS as their height increased. Moreover, patients with heights between 165 and 179 cm had a better OS compared to other patients (P = .05). This effect was independent of treatment arm and gender. CONCLUSION: Patients shorter than 165 cm and taller than 179 cm have a worse OS, while those between 165 and 179 cm have a better OS. Hence, clinicians should consider height as an important prognostic factor when treating metastatic CRC patients. Future prospective studies are warranted to shed light on the mechanisms underlying the worse OS in taller patients.

Outlooks on Epstein-Barr virus associated gastric cancer.

Epstein-Barr virus associated gastric cancer (EBVaGC) comprises approximately 10% of gastric carcinomas. Multiple factors contribute to tumorigenesis, including EBV driven hypermethylation of tumor suppressor genes, inflammatory changes in gastric mucosa, host immune evasion by EBV and changes in cell cycle pathways. The unique molecular characteristics of EBVaGC, such as programmed death ligand 1 (PD-L1) overexpression, highlight the potential for using EBV as a biomarker for response to immunotherapy. Few studies have reported benefit from immunotherapy in EBV positive cancers, and clinical trials investigating the impact of checkpoint inhibitors in EBVaGC are currently underway. This review provides the most recent updates on molecular pathophysiology, epidemiology, clinical features and treatment advances pertaining to EBVaGC.

Pharmacogenomics in colorectal cancer: current role in clinical practice and future perspectives.

The treatment scenario of colorectal cancer (CRC) has been evolving in recent years with the introduction of novel targeted agents and new therapeutic strategies for the metastatic disease. An extensive effort has been directed to the identification of predictive biomarkers to aid patients selection and guide therapeutic choices. Pharmacogenomics represents an irreplaceable tool to individualize patients treatment based on germline and tumor acquired somatic genetic variations able to predict drugs response and risk of toxicities. The growing knowledge of CRC molecular characteristics and complex genomic makeup has played a crucial role in identifying predictive pharmacogenomic biomarkers, while supporting the rationale for the development of new drugs and treatment combinations. Clinical validation of promising biomarkers, however, is often an issue. More recently, a deeper understanding of resistance mechanisms and tumor escape dynamics under treatment pressure and the availability of novel technologies are opening new perspectives in this field. This review aims to present an overview of current pharmacogenomic biomarkers and future perspectives of pharmacogenomics in CRC, in an evolving scenario moving from a single drug-gene interactions approach to a more comprehensive genome-wide approach, comprising genomics and epigenetics.

CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - A target for novel cancer therapy.

Chemokines are proteins which induce chemotaxis, promote differentiation of immune cells, and cause tissue extravasation. Given these properties, their role in anti-tumor immune response in the cancer environment is of great interest. Although immunotherapy has shown clinical benefit for some cancer patients, other patients do not respond. One of the mechanisms of resistance to checkpoint inhibitors may be chemokine signaling. The CXCL9, -10, -11/CXCR3 axis regulates immune cell migration, differentiation, and activation, leading to tumor suppression (paracrine axis). However, there are some reports that show involvements of this axis in tumor growth and metastasis (autocrine axis). Thus, a better understanding of CXCL9, -10, -11/CXCR3 axis is necessary to develop effective cancer control. In this article, we summarize recent evidence regarding CXCL9, CXCL10, CXCL11/CXCR3 axis in the immune system and discuss their potential role in cancer treatment.

Colorectal cancer: epigenetic alterations and their clinical implications.

Colorectal cancer (CRC) is a heterogeneous disease with distinct molecular and clinical features, which reflects the wide range of prognostic outcomes and treatment responses observed among CRC patients worldwide. Our understanding of the CRC epigenome has been largely developed over the last decade and it is now believed that among thousands of epigenetic alterations present in each tumor, a small subgroup of these may be considered as a CRC driver event. DNA methylation profiles have been the most widely studied in CRC, which includes a subset of patients with distinct molecular and clinical features now categorized as CpG island methylator phenotype (CIMP). Major advances have been made in our capacity to detect epigenetic alterations, providing us with new potential biomarkers for diagnostic, prognostic and therapeutic purposes. This review aims to summarize our current knowledge about epigenetic alterations occurring in CRC, underlying their potential future clinical implications in terms of diagnosis, prognosis and therapeutic strategies for CRC patients.