Steven M. Cohen

Dendritic Cells Promote Pancreatic Viability in Mice with Acute Pancreatitis

BACKGROUND & AIMSnThe cellular mediators of acute pancreatitis are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis.nnnMETHODSnAcute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier method.nnnRESULTSnNumbers of major histocompatibility complex II(+)CD11c(+) DCs increased 100-fold in pancreata of mice with acute pancreatitis to account for nearly 15% of intrapancreatic leukocytes. Intrapancreatic DCs acquired a distinct immune phenotype in mice with acute pancreatitis; they expressed higher levels of major histocompatibility complex II and CD86 and increased production of interleukin-6, membrane cofactor protein-1, and tumor necrosis factor-α. However, rather than inducing an organ-destructive inflammatory process, DCs were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DCs and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DCs died from acinar cell death within 4 days. Depletion of DCs from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DCs did not require infiltrating neutrophils, activation of nuclear factor-κB, or signaling by mitogen-activated protein kinase or tumor necrosis factor-α.nnnCONCLUSIONSnDCs are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress.

Team Play in Surgical Education: A Simulation-Based Study

BACKGROUNDnSimulation-based training provides a low-stress learning environment where real-life emergencies can be practiced. Simulation can improve surgical education and patient care in crisis situations through a team approach emphasizing interpersonal and communication skills.nnnOBJECTIVEnThis study assessed the effects of simulation-based training in the context of trauma resuscitation in teams of trainees.nnnMETHODSnIn a New York State-certified level I trauma center, trauma alerts were assessed by a standardized video review process. Simulation training was provided in various trauma situations followed by a debriefing period. The outcomes measured included the number of healthcare workers involved in the resuscitation, the percentage of healthcare workers in role position, time to intubation, time to intubation from paralysis, time to obtain first imaging study, time to leave trauma bay for computed tomography scan or the operating room, presence of team leader, and presence of spinal stabilization. Thirty cases were video analyzed presimulation and postsimulation training. The two data sets were compared via a 1-sided t test for significance (p < 0.05). Nominal data were analyzed using the Fischer exact test.nnnRESULTSnThe data were compared presimulation and postsimulation. The number of healthcare workers involved in the resuscitation decreased from 8.5 to 5.7 postsimulation (p < 0.001). The percentage of people in role positions increased from 57.8% to 83.6% (p = 0.46). The time to intubation from paralysis decreased from 3.9 to 2.8 minutes (p < 0.05). The presence of a definitive team leader increased from 64% to 90% (p < 0.05). The rate of spine stabilization increased from 82% to 100% (p < 0.08). After simulation, training adherence to the advanced trauma life support algorithm improved from 56% to 83%.nnnCONCLUSIONSnHigh-stress situations simulated in a low-stress environment can improve team interaction and educational competencies. Providing simulation training as a tool for surgical education may enhance patient care.

Fatal falls in New York City: an autopsy analysis of injury patterns

IntroductionFalls from heights are an important cause of unintentional fatal injury. We investigated the relationship between the characteristics of fatal falls and resulting injury patterns. Materials and MethodsWe reviewed prospectively collected data from the Office of Chief Medical Examiner in New York City between 2000 and 2010. Data included fall height, work or non–work related, use of safety equipment, intentionality, specific organ injuries, and death on impact. The primary outcome was organ injury based on fall height. ResultsHigher falls were associated with hemorrhage as well as rib and various organ injuries. Organ injury pattern did not differ based on work status. The presence of equipment misuse or malfunction was associated with more deaths upon impact. Victims of falls from 200 ft or higher were 11.59 times more likely to die on impact than from lower than 25 ft. ConclusionsFall height and work-related falls were significantly associated with death on impact. This is a public health issue, as 13% of falls were work related and 4% of falls were due to improper use of safety equipment. Some work-related falls are potentially preventable with proper safety equipment use. Understanding patterns of injury may play a role in prevention and management of survivors in the acute period.

Abstract 101: Pilot study of oral microbiome and risk of pancreatic cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCnnPrevious studies showed that periodontitis and tooth loss are associated with increased risk of pancreatic cancer, suggesting possible role of oral bacteria in the pancreatic cancer etiology. We evaluated whether oral microbiome is associated with risk of pancreatic cancer and pancreatitis.nnOral wash samples were collected from 13 pancreatic cancer patients, 3 pancreatitis patients and 12 healthy controls at NYU Langone Medical Center, New York. Ribosomal 16S rRNA genes from oral wash DNA were amplified by universal primers, barcoded, and sequenced with 454 FLX technology. The bacterial 16S rRNA gene sequences were binned into operational taxonomic units (OTUs) with 97% identify and further classified by taxonomy. Non-parametric Wilcoxon Mann Whiteney U test and Kuskal-Wallis test were conducted to compare the relative abundance of taxa across pancreatic cancer, pancreatitis and control groups.nnA total of 250,008 sequence reads (average 8,928 reads per sample) were observed. Firmicutes, Bacteroidetes, and Actinobacteria are major phyla, accounting for 96.5% of oral microbiota. We found that bacteroides genus was significantly more abundant in both pancreatic cancer patients (p = 0.002) and pancreatitis patients (p = 0.004) compared with control group. Further, BLAST search results indicate that the species most closely represented by the Bacteroides OTUs were oral pathogen. In addition, Corynebacterium (p = 0.033) and Aggregatibacter (p = 0.019) were less abundant in pancreatic cancer and pancretitis groups compared with controls.nnData from this pilot study of oral microbiome and pancreatic cancer suggest that the differential abundance in bacteriodates and possibly Corynebacterium and Aggregatibacter, are associated with risk of pancreatic cancer. Bacteroides, Gram-negative bacillus bacteria, plays an important role in oral inflammation, including periodontitis. Further larger studies are warranted to confirm these preliminary findings.nnCitation Format: I-Hsin Lin, Jing Wu, Steven M. Cohen, Calvin Chen, Darren Bryk, Mollie Marr, Marcovalerio Melis, Elliot Newman, H Leon Pachter, Alexander V. Alekseyenko, Richard B. Hayes, Jiyoung Ahn. Pilot study of oral microbiome and risk of pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 101. doi:10.1158/1538-7445.AM2013-101