The last days: The medical response of United States and allied military teams during the Afghanistan Exodus.

OBJECTIVES: The objective of this study is to describe the United States and allied military medical response during the withdrawal from Afghanistan. BACKGROUND: The military withdrawal from Afghanistan concluded with severe hostilities resulting in numerous civilian and military casualties. The clinical care provided by coalition forces capitalized on decades of lessons learned and enabled unprecedented accomplishments. METHODS: In this retrospective, observational analysis, casualty numbers, and operative information was collected and reported from military medical assets in Kabul, Afghanistan. The continuum of medical care and the trauma system, from the point of injury back to the United States was captured and described. RESULTS: Prior to a large suicide bombing resulting in a mass casualty event, the international medical teams managed distinct 45 trauma incidents involving nearly 200 combat and non-combat civilian and military patients over the preceding 3 months. Military medical personnel treated 63 casualties from the Kabul airport suicide attack and performed 15 trauma operations. US air transport teams evacuated 37 patients within 15 hours of the attack. CONCLUSION: Lessons learned from the last 20 years of combat casualty care were successfully implemented during the culmination of the Afghanistan conflict. Ultimately, the effort, teamwork, and system adaptability exemplify not only the attitudes and character of service members who provide modern combat casualty care but also the paramount importance of the battlefield learning health care system. A continued posture to maintain military surgical preparedness in unique environments remain crucial as the US military prepares for the future.Retrospective observational analysis. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.

Development of an emergency general surgery process improvement program.

BACKGROUND: The Joint Trauma System has demonstrated improved outcomes through coordinated research and process improvement programs. With fewer combat trauma patients, our military American College of Surgeons level 2 trauma center's ability to maintain a strong trauma Process Improvement (PI) program has become difficult. As emergency general surgery (EGS) patients are similar to trauma patients, our Trauma and Acute Care Surgery (TACS) service developed an EGS PI program analogous to what is done in trauma. We describe the implementation of our novel EGS PI program and its effect on institutional PI proficiency. METHODS: An EGS registry was developed in 2013. Inclusion criteria were based on AAST published literature. In 2015, EGS registrar and PI coordinator positions were developed and filled with existing trauma staff. A formal EGS PI program began January 1, 2016. Pre- and post-program data was compared to determine the effect including EGS PI events had on increasing yield into our trauma PI program. RESULTS: In 2016, TACS saw 1001 EGS consults. Four hundred forty-four met criteria for registry inclusion. Eighty-two patients had 131 PI events; re-admission within 30 days, unplanned therapeutic intervention, and unplanned ICU admission were the most common events. Capture of EGS PI events yielded a 49% increase compared with 2015. CONCLUSION: Overall patient volume and PI events post EGS PI program initiation exceeded those prior to implementation. These data suggest that extending trauma PI principles to EGS may be beneficial in maintaining inter-war military and/or lower volume trauma center readiness.

Evaluation and management of pilonidal disease.

Pilonidal disease is a common condition, ranging from the routine cyst with abscess to extensive chronic infection and sinus formation. It can be associated with significant morbidity and prolonged wound healing after definitive surgery. This article reviews the history and pathogenesis of this often challenging surgical problem and the numerous nonoperative and operative treatment options currently available for it.

Tobacco smoke induces polycomb-mediated repression of Dickkopf-1 in lung cancer cells.

Limited information is available about epigenetic mechanisms by which cigarette smoke enhances the initiation and progression of lung cancer. To examine this issue, A549 and Calu-6 lung cancer cells were cultured in normal media with or without tobacco smoke condensate (TSC) under clinically relevant exposure conditions. Ten-day TSC exposure dramatically increased the tumorigenicity of lung cancer cells in nude mice. Microarray and quantitative reverse transcription-PCR (RT-PCR) experiments revealed that this phenomenon coincided with diminished expression of Dickkopf-1 (Dkk-1). Western blot, chromatin immunoprecipitation, methylation-specific PCR, and pyrosequencing experiments showed that repression of Dkk-1 coincided with decreased H4K16Ac, increased H3K27me3, and recruitment of SirT1, EZH2, SUZ12, and Bmi1 without DNA hypermethylation within the Dkk-1 promoter despite prolonged TSC exposures. Removal of TSC from culture media resulted in loss of promoter-associated polycomb repressor complexes and reexpression of Dkk-1. siRNA-mediated knockdown of EZH2 and SirT1 partially abrogated TSC-mediated inhibition of Dkk-1 expression. Western blot and quantitative RT-PCR array experiments showed that TSC exposure as well as knockdown of Dkk-1 activated Wnt signaling and significantly up-regulated Wnt5a in lung cancer cells. Knockdown of Dkk-1 recapitulated the dramatic protumorigenic effects of TSC exposure in Calu-6 cells. Despite the transient nature of Dkk-1 repression following TSC exposure in vitro, Dkk-1 remained silenced in tumor xenografts derived from TSC-treated Calu-6 cells. Collectively, these data provide evidence that cigarette smoke directly engages polycomb machinery to activate a signaling network implicated in maintenance of cancer stem cells.

Aurora A, Aurora B and survivin are novel targets of transcriptional regulation by histone deacetylase inhibitors in non-small cell lung cancer.

BACKGROUND: Analysis of biopsies from a recent clinical trial suggested that Depsipeptide FK228 (DP) inhibits Aurora kinase expression in lung cancer cells. The present study was undertaken to confirm and extend these observations. RESULTS: Aurora A and B mRNA levels in lung cancer cells were considerably higher than levels in normal pulmonary epithelia. DP, TSA and SAHA inhibited Aurora A, Aurora B and survivin expression with kinetics that were remarkably similar within individual cell lines, and appeared to coincide with p53 expression status. These effects were not observed following treatment with geldanamycins. Inhibition of Aurora B transcription coincided with decreased H3K9Ac and H3K4Me2 activation marks, and accumulation of H3K9Me3, as well as MBD1, MBD2 and MBD3 repression marks within the minimal Aurora B promoter. Knockdown of MBD1, -2 or -3 did not reproducibly abrogate inhibition of Aurora or survivin expression by DP or TSA. DP and TSA decreased expression and altered localization of Aurora kinases and survivin, resulting in mitotic catastrophe in lung cancer cells. METHODS: Aurora A, and Aurora B levels in lung cancer cells and normal respiratory epithelia were assessed using quantitative RT-PCR techniques. These methods, as well as as Western blots were used to examine expression of Auroras A/B, and several related genes/proteins in lung cancer cells exposed to DP, TSA, SAHA and geldanamycins. Transient transfection promoter-reporter assays, and chromatin immunoprecipitation (ChIP) techniques were used to examine DP-mediated changes in activity and chromatin structure of the Aurora B promoter. Confocal imaging techniques were used to examine the effects of DP and TSA on mitotic progression in lung cancer cells. CONCLUSIONS: Novel transcriptional regulatory mechanisms involving Aurora kinase and survivin appear to contribute to cytotoxicity mediated by HDAC inhibitors in lung cancer cells.