The consequences of noncompliance with guidelines for withholding or terminating resuscitation in traumatic cardiac arrest patients.

BACKGROUND: The validity of current guidelines regarding resuscitation of patients in traumatic cardiopulmonary arrest (TCPA) and the ability of emergency medical services (EMS) to appropriately apply them have been called into question. The purpose of this study is to demonstrate the consequences of violating the current published guidelines and whether EMS personnel were able to accurately identify patients in TCPA. METHODS: We conducted a retrospective review of our Level I trauma center's database that identified 294 patients over an 8-year period (January 1, 2003, to December 31, 2010) who suffered prehospital TCPA and met criteria for the withholding or termination of resuscitation based on current guidelines. Patient demographics, prehospital/emergency department physiology, survival, neurologic outcome, and hospital charges were analyzed. RESULTS: One of 294 patients (0.3%) survived to reach hospital discharge with a Glasgow Coma Scale score of 6. The total costs incurred for these 294 patients meeting criteria for withholding or termination of resuscitation were $3,852,446.65. One hundred seventeen (39.8%) patients were evaluated by more than one EMS team. There was 100% agreement on the presence (15 of 15) or absence (102 of 102) of a pulse between the EMS teams. CONCLUSIONS: Our data support the current guidelines regarding the withholding or termination of resuscitation of patients in prehospital TCPA and represent the largest series to date on this topic. EMS personnel were able to accurately determine traumatic cardiac arrest in the field in this series. Violation of the current guidelines resulted in six patients being resuscitated to a neurologically devastated state. No loss of neurologically intact survivors would have resulted had strict adherence to the guidelines been maintained.

Aberrant crypt foci.

Colon cancer evolves through epithelial cell deregulation and inappropriate proliferation. These histopathological characteristics are exemplified in the biochemical, immunohistochemical, genetic and epigenetic elements detected within colonic mucosa. Early detection is paramount for the prevention of colon cancer deaths. Aberrant crypt foci (ACF) are thought to be the earliest identifiable neoplastic lesions in the colon carcinogenetic model. The progression of ACF to polyp and, subsequently, to cancer parallels the accumulation of several biochemical alterations and mutations whereby a small fraction of ACF evolve to colon cancer. Recent data indicate that, not uncommonly, some ACF bypass the polyp stage in their carcinogenesis thus reinforcing the importance of their early detection and our understanding of their pathogenesis. Since ACF were first detected in carcinogen-treated mice, research efforts have focused on these microscopically visible lesions both in animal and human models. ACF show variable histological features, characterized by Kudo (20) and, therefore, can be grouped into differing categories by in vivo examination with high-magnification-chromoscopic-colonoscopy (HMCC). As expected, ACF are more frequently detected in distal animal and human colons coinciding with the geographic distribution of colorectal cancer (CRC). Various proteomic (Prot) markers may be altered within ACF suggesting possible prospective pathological changes. These markers include Calreticulin, Transgelin, Serotransferrin, Triphosphate isomerase and Carbonic anhydrase II. Other markers of importance include carcinoembryonic antigen (CEA), B-catenin, placental cadherin (P-cadherin), epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2) and P16INK4a. Genetic mutations of K-ras, B-Raf APC and p53 have been demonstrated in ACF as well as the epigenetic alterations of CpG island methylation. Genomic instabilities (GI), illustrated by a higher GI Index (GII), microsatellite instability (MSI), loss of heterozygosity (LOH) and defects in mismatch repair (MMR) systems, are also expressed. These transformations may lead to the identification of the earliest pathological features initiating colon tumorigenesis. In this review, the advances in ACF research as precursors of CRCs are highlighted.

Sulindac enhances tumor necrosis factor-alpha-mediated apoptosis of lung cancer cell lines by inhibition of nuclear factor-kappaB.

Programmed cell death (apoptosis) is induced by certain anticancer therapies, and resistance to apoptosis is a major mechanism by which tumors evade these therapies. The transcription factor nuclear factor (NF)-kappaB, which is frequently activated by treatment of cancer cells with different chemotherapeutic agents, promotes cell survival, whereas its inhibition leads to enhanced apoptosis. Recently, sulindac and other nonsteroidal anti-inflammatory drugs have been shown to inhibit tumor necrosis factor (TNF)-alpha-mediated NF-kappaB activation. Here, we demonstrate that treatment of the non-small cell lung carcinoma cells NCI-H157 and NCI-H1299 with sulindac greatly enhances TNF-alpha-mediated apoptosis. We further show that sulindac inhibits TNF-alpha-mediated activation of NF-kappaB DNA binding and nuclear translocation of NF-kappaB. These results suggest that sulindac and other nonsteroidal anti-inflammatory drug inhibitors of NF-kappaB activation may serve as useful agents in cancer chemotherapy.