Upregulation of the microRNA cluster at the Dlk1-Dio3 locus in lung adenocarcinoma.

Mice in which lung epithelial cells can be induced to express an oncogenic Kras(G12D) develop lung adenocarcinomas in a manner analogous to humans. A myriad of genetic changes accompany lung adenocarcinomas, many of which are poorly understood. To get a comprehensive understanding of both the transcriptional and post-transcriptional changes that accompany lung adenocarcinomas, we took an omics approach in profiling both the coding genes and the non-coding small RNAs in an induced mouse model of lung adenocarcinoma. RNAseq transcriptome analysis of Kras(G12D) tumors from F1 hybrid mice revealed features specific to tumor samples. This includes the repression of a network of GTPase-related genes (Prkg1, Gnao1 and Rgs9) in tumor samples and an enrichment of Apobec1-mediated cytosine to uridine RNA editing. Furthermore, analysis of known single-nucleotide polymorphisms revealed not only a change in expression of Cd22 but also that its expression became allele specific in tumors. The most salient finding, however, came from small RNA sequencing of the tumor samples, which revealed that a cluster of ∼53 microRNAs and mRNAs at the Dlk1-Dio3 locus on mouse chromosome 12qF1 was markedly and consistently increased in tumors. Activation of this locus occurred specifically in sorted tumor-originating cancer cells. Interestingly, the 12qF1 RNAs were repressed in cultured Kras(G12D) tumor cells but reactivated when transplanted in vivo. These microRNAs have been implicated in stem cell pleuripotency and proteins targeted by these microRNAs are involved in key pathways in cancer as well as embryogenesis. Taken together, our results strongly imply that these microRNAs represent key targets in unraveling the mechanism of lung oncogenesis.

Safety and efficacy of early surgical decompression of the thoracic outlet for Paget-Schroetter syndrome.

The surgical treatment of Paget-Schroetter syndrome has evolved to include early thrombolytic therapy and an interval period of anticoagulation, followed by late surgical decompression of the thoracic outlet. More recently, we have developed an abbreviated course of therapy in which the thrombolytic therapy is followed by early surgical decompression during the same admission, then a period of anticoagulation. We compared early surgical decompression with the standard management protocol to determine safety and efficacy of the early treatment algorithm. Nine patients were treated with lysis and early operation. These were compared with the preceding nine consecutive patients treated with lysis and staged operation. Demographic data, risk factors, duration of thrombosis, lytic therapy, time to surgery, operative variables, and postoperative complications were analyzed. Our results showed that thrombolysis followed by early operation does not result in increased perioperative morbidity or mortality. Early surgical decompression of the thoracic outlet during the same admission as lysis is as safe and efficacious as the traditional (staged decompression) approach to Paget-Schroetter syndrome. Lysis followed by early surgical decompression should be considered a new standard of care in the management of Paget-Schroetter syndrome.

Improving pain management in critical care.

BACKGROUND: In April 1994 at the University of California at Los Angeles Medical Center the Surgical Intensive Care Unit's (SICU's) Quality Improvement Council unanimously agreed on pain management as one of the major factors that negatively affect outcomes for their patient population. Using the FOCUS-PDCA (plan-do-check-act) model for quality improvement (QI), the council chartered a subcommittee to improve the pain management in their ICUs. METHODOLOGY: The subcommittee first measured the pain assessment scores of patients at transfer from the ICU. After ascertaining that these scores were greater than the goal of 2, the process of providing pain relief was examined with the assistance of process control statistics, which showed a process barely capable of meeting the goal of pain score of 2 or less on a 0-5 scale. The process factors that affected this outcome were examined and changes were made where appropriate. One of these changes was development of a guideline for acute pain management based on the Agency for Health Care Policy Research's Acute Pain Management Clinical Practice Guideline. Reassessment of the pain scores and the process was then conducted. RESULTS: The pain assessment scores at transfer from the ICU decreased significantly. Thirty-five percent of patients in the preguideline survey rated their scores as greater than 2, compared with only 21% at the postguideline survey. Pain assessment and documentation also improved significantly. CONCLUSION: The Quality Improvement Council felt that improvements in pain management were due largely to their having provided staff with the right tools to use in assessing, documenting, and controlling pain. Gains in pain management continue to be made.

Thromboembolic phenomena.

Venous thrombosis and thromboembolic phenomenon affect over 2 million people each year. Estimates indicate that there are 50,000 deaths from pulmonary embolus annually and that this number has not declined in 20 years. Understanding the etiology and prevention of this complication is essential to the critical care health care practitioner.