Simulation-based assessment and retraining for the anesthesiologist seeking reentry to clinical practice: a case series.

Background: Established models for assessment and maintenance of competency in anesthesiology may not be adequate for anesthesiologists wishing to reenter practice. The authors describe a program developed in their institution incorporating simulator-based education, to help determine competency in licensed and previously licensed anesthesiologists before return to practice.

Methods: The authors have used simulation for assessment and retraining at their institution since 2002.

Combining radiotherapy and cancer immunotherapy: a paradigm shift.

The therapeutic application of ionizing radiation has been largely based on its cytocidal power combined with the ability to selectively target tumors. Radiotherapy effects on survival of cancer patients are generally interpreted as the consequence of improved local control of the tumor, directly decreasing systemic spread. Experimental data from multiple cancer models have provided sufficient evidence to propose a paradigm shift, whereby some of the effects of ionizing radiation are recognized as contributing to systemic antitumor immunity.

Invariant NKT cells as novel targets for immunotherapy in solid tumors.

Natural killer T (NKT) cells are a small population of lymphocytes that possess characteristics of both innate and adaptive immune cells. They are uniquely poised to respond rapidly to infection and inflammation and produce cytokines that critically shape the ensuing adaptive cellular response. Therefore, they represent promising therapeutic targets.

Radiation as an immunological adjuvant: current evidence on dose and fractionation.

Ionizing radiation to a cancer site has the ability to convert the irradiated tumor in an immunogenic hub. However, radiation is a complex modifier of the tumor microenvironment and, by itself, is seldom sufficient to induce a therapeutically significant anti-tumor immune response, since it can also activate immune suppressive pathways. While several combinations of local radiation and immunotherapy have been shown in pre-clinical models to induce powerful anti-tumor immunity, the optimal strategy to achieve this effect remains to be defined.

Synergy of topical toll-like receptor 7 agonist with radiation and low-dose cyclophosphamide in a mouse model of cutaneous breast cancer.

Purpose: This study tested the hypothesis that topical Toll-like receptor (TLR) 7 agonist imiquimod promotes antitumor immunity and synergizes with other treatments in a model of skin-involving breast cancer.

Experimental Design: TSA mouse breast carcinoma cells were injected s.c.

Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects.

A promising strategy for cancer immunotherapy is to disrupt key pathways regulating immune tolerance, such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4). However, the determinants of response to anti-CTLA-4 mAb treatment remain incompletely understood. In murine models, anti-CTLA-4 mAbs alone fail to induce effective immune responses to poorly immunogenic tumors but are successful when combined with additional interventions, including local ionizing radiation (IR) therapy.

Role of T lymphocytes in tumor response to radiotherapy.

Over thirty years ago, Helen Stone and colleagues compared the effects of local tumor irradiation in immunocompetent and T cell deficient mice, providing the first evidence that tumor response to radiotherapy is impaired in the absence of a normal T cell repertoire. In the following three decades there has been an exponential growth in understanding T cells and the complex molecular mechanisms that regulate their activation, migration to tumors and effector functions. We now also know that tumor progression is intrinsically linked to the development of multiple immunosuppressive mechanisms that allow cancer cells to escape immune control.

The convergence of radiation and immunogenic cell death signaling pathways.

Ionizing radiation (IR) triggers programmed cell death in tumor cells through a variety of highly regulated processes. Radiation-induced tumor cell death has been studied extensively in vitro and is widely attributed to multiple distinct mechanisms, including apoptosis, necrosis, mitotic catastrophe (MC), autophagy, and senescence, which may occur concurrently. When considering tumor cell death in the context of an organism, an emerging body of evidence suggests there is a reciprocal relationship in which radiation stimulates the immune system, which in turn contributes to tumor cell kill.

Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer.

Purpose: Skin metastases of breast cancer remain a therapeutic challenge. Toll-like receptor 7 agonist imiquimod is an immune response modifier and can induce immune-mediated rejection of primary skin malignancies when topically applied. Here we tested the hypothesis that topical imiquimod stimulates local antitumor immunity and induces the regression of breast cancer skin metastases.

The influence of simulation-based physiology labs taught by anesthesiologists on the attitudes of first-year medical students towards anesthesiology.

Background: The development of medical students' perceptions of different medical specialties is based on many factors and influences their career choices and appreciation of other practitioners' knowledge and skills. The goal of this study was to determine if participation in a series of anesthesiologist-run, simulation-based physiology labs changed first year medical students' perceptions of anesthesiologists.

Methods: One hundred first-year medical students were surveyed at random three months before completion of a simulation-based physiology lab run by anesthesiologists.

Bilateral sphenopalatine ganglion blockade improves postoperative analgesia after endoscopic sinus surgery.

Background: Endoscopic sinus surgery (ESS) is a common procedure preferably done with an anesthetic technique ensuring effective postoperative analgesia while speeding discharge home. Although anesthesia administered locally in conjunction with vasoconstricting agents is known to minimize intraoperative bleeding, its usefulness in providing postoperative analgesia has not been well characterized. The results supporting the use of regional anesthesia for sinus surgery have also been limited.

Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during eye development.

Tissue fusion is an essential morphogenetic mechanism in development, playing a fundamental role in developing neural tube, palate and the optic fissure. Disruption of genes associated with the tissue fusion can lead to congenital malformations, such as spina bifida, cleft lip/palate and ocular coloboma. For instance, the Pax2 transcription factor is required for optic fissure closure, although the mechanism of Pax2 action leading to tissue fusion remains elusive.

Simulation-based Maintenance of Certification in Anesthesiology (MOCA) course optimization: use of multi-modality educational activities.

In 2010, the American Board of Anesthesiology instituted a new Maintenance of Certification in Anesthesiology (MOCA) Part IV activity requiring diplomates to attend and self-reflect on a simulation-based course in an American Society of Anesthesiologists-endorsed program. Although there are certain course requirements, much of the curriculum and structure of these MOCA activities is left to the discretion of the participating endorsed program. The ideal course would emphasize multimodality simulation-based activities that optimize diplomate education and satisfaction, while economizing faculty requirements.

Role of simulation in U.S. physician licensure and certification.

The evolution of simulation from an educational tool to an emerging evaluative tool has been rapid. Physician certification has a long history and serves an important role in assuring that practicing physicians are competent and capable of providing a high level of safe care to patients. Traditional assessment methods have relied mostly on multiple-choice exams or continuing medical education exercises.

TGFβ1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo.

Purpose: To determine whether inhibition of TGFβ signaling prior to irradiation sensitizes human and murine cancer cells in vitro and in vivo.

Experimental Design: TGFβ-mediated growth and Smad phosphorylation of MCF7, Hs578T, MDA-MB-231, and T47D human breast cancer cell lines were examined and correlated with clonogenic survival following graded radiation doses with and without pretreatment with LY364947, a small molecule inhibitor of the TGFβ type I receptor kinase. The DNA damage response was assessed in irradiated MDA-MB-231 cells pretreated with LY364947 in vitro and LY2109761, a pharmacokinetically stable inhibitor of TGFβ signaling, in vivo.

Use of the BATHE method in the preanesthetic clinic visit.

Background: In the primary care setting, use of the BATHE (Background, Affect, Trouble, Handling, and Empathy) method of interviewing has been shown to increase patient satisfaction. This technique is a brief psychotherapeutic method used to address patients' physical and psychosocial problems. The BATHE technique has not been evaluated in the perioperative setting as a way of improving patient satisfaction.

Defining the role of the immune system in cancer treatment: highlights from the Immunochemotherapy Conference.

The Immunochemotherapy: Correcting Immune Escape in Cancer meeting was co-organized by George Prendergast (Lankenau Institute for Medical Research, PA, USA), Guido Kroemer (Gustave Roussy Cancer Institute, Paris, France) and Laurence Zitvogel (Gustave Roussy Cancer Institute) in partnership with Abcam. It brought together investigators with a diverse background in immunology, oncology and cancer biology, and offered a forum for discussion of a new vision that acknowledges the role of the host immune system not only in cancer development and progression, but also as a major determinant of response to treatment. An important implication of this vision is that synergy between conventional cytocidal modalities and immune response modifiers is not only possible, but holds the promise to revolutionize cancer treatment.

The numbers of FoxP3+ lymphocytes in sentinel lymph nodes of breast cancer patients correlate with primary tumor size but not nodal status.

Regulatory T cells, lymphocytes marked by expression of the transcription factor Forkhead Box Protein P3 (FoxP3), inhibit the activation of tumor-specific T cells in tumor-draining lymph nodes. Immunohistochemical analyses of sentinel lymph nodes (SLNs) from 104 breast cancer patients showed a significant association (p = .0028, Pearson correlation) between the number of FoxP3+ cells and the size of primary breast invasive ductal carcinoma.

Missed steps in the preanesthetic set-up.

Background: Anesthesiologists accomplish many tasks rapidly during induction of an anesthetic. Key preparation for induction is needed to maximize patient safety. Given the intense environment of the operating room, preparatory steps may be missed either unintentionally or possibly even intentionally to save time.

Expression of cancer testis antigens in human BRCA-associated breast cancers: potential targets for immunoprevention?

Introduction: Novel breast cancer risk-reducing strategies for individuals with germline mutations of the BRCA1 and/or BRCA2 genes are urgently needed. Identification of antigenic targets that are expressed in early cancers, but absent in normal breast epithelium of these high-risk individuals, could provide the basis for the development of effective immunoprophylactic strategies. Cancer testis (CT) antigens are potential candidates because their expression is restricted to tumors, and accumulating data suggest that they play important roles in cellular proliferation, stem cell function, and carcinogenesis.

The cell biology of smell.

The olfactory system detects and discriminates myriad chemical structures across a wide range of concentrations. To meet this task, the system utilizes a large family of G protein-coupled receptors-the odorant receptors-which are the chemical sensors underlying the perception of smell. Interestingly, the odorant receptors are also involved in a number of developmental decisions, including the regulation of their own expression and the patterning of the olfactory sensory neurons' synaptic connections in the brain.