Validation of a Simulation-Based Resuscitation Curriculum for Maternal Cardiac Arrest.

OBJECTIVE: To assess the knowledge, skills, and self-efficacy of health care participants completing a simulation-based blended learning training curriculum on managing maternal medical emergencies and maternal cardiac arrest (Obstetric Life Support). METHODS: A formative assessment of the Obstetric Life Support curriculum was performed with a prehospital cohort comprising emergency medical services professionals and a hospital-based cohort comprising health care professionals who work primarily in hospital or urgent care settings and respond to maternal medical emergencies. The training consisted of self-guided precourse work and an instructor-led simulation course using a customized low-fidelity simulator. Baseline and postcourse assessments included multiple-choice cognitive test, self-efficacy questionnaire, and graded Megacode assessment of the team leader. Megacode scores and pass rates were analyzed descriptively. Pre- and post-self-confidence assessments were compared with an exact binomial test, and cognitive scores were compared with generalized linear mixed models. RESULTS: The training was offered to 88 participants between December 2019 and November 2021. Eighty-five participants consented to participation; 77 participants completed the training over eight sessions. At baseline, fewer than half of participants were able to achieve a passing score on the cognitive assessment as determined by the expert panel. After the course, mean cognitive assessment scores improved by 13 points, from 69.4% at baseline to 82.4% after the course (95% CI 10.9-15.1, P <.001). Megacode scores averaged 90.7±6.4%. The Megacode pass rate was 96.1%. There were significant improvements in participant self-efficacy, and the majority of participants (92.6%) agreed or strongly agreed that the course met its educational objectives. CONCLUSION: After completing a simulation-based blended learning program focused on managing maternal cardiac arrest using a customized low-fidelity simulator, most participants achieved a defensible passing Megacode score and significantly improved their knowledge, skills, and self-efficacy.

Soluble fibrin inhibits lymphocyte adherence and cytotoxicity against tumor cells: implications for cancer metastasis and immunotherapy.

Circulating soluble fibrin (sFn) is elevated in many cancer patients. It is a marker for ongoing disseminated intravascular coagulation and may have prognostic significance. We have demonstrated that sFn inhibited monocyte adherence and cytotoxicity by a mechanism involving blockade of monocyte alphaMbeta2 and tumor cell CD54. It was, therefore, hypothesized that sFn also inhibits lymphocyte and interleukin-2-activated lymphocyte (LAK) adherence and cytotoxicity against tumor cells. This study sought to identify the lymphocyte subset responsible for adherence and killing of A375 melanoma cells and whether sFn inhibited these parameters. Lymphocyte and LAK cell adherence and cytotoxicity, which was adherence dependent, were inhibited by preincubation with purified or plasma-derived sFn. The lymphocyte and LAK cell activities were primarily a result of CD8(+) MHC (major histocompatibility complex) unrestricted cytotoxic T cells. These results suggest that elevated levels of circulating sFn may be immunosuppressive and may reduce the efficacy of adoptive immunotherapies.

Soluble fibrin inhibits monocyte adherence and cytotoxicity against tumor cells: implications for cancer metastasis.

BACKGROUND: Soluble fibrin (sFn) is a marker for disseminated intravascular coagulation and may have prognostic significance, especially in metastasis. However, a role for sFn in the etiology of metastatic cancer growth has not been extensively studied. We have reported that sFn cross-linked platelet binding to tumor cells via the major platelet fibrin receptor alphaIIb beta3, and tumor cell CD54 (ICAM-1), which is the receptor for two of the leukocyte beta2 integrins (alphaL beta2 and aM beta2). We hypothesized that sFn may also affect leukocyte adherence, recognition, and killing of tumor cells. Furthermore, in a rat experimental metastasis model sFn pre-treatment of tumor cells enhanced metastasis by over 60% compared to untreated cells. Other studies have shown that fibrin(ogen) binds to the monocyte integrin alphaM beta2. This study therefore sought to investigate the effect of sFn on beta2 integrin mediated monocyte adherence and killing of tumor cells. METHODS: The role of sFn in monocyte adherence and cytotoxicity against tumor cells was initially studied using static microplate adherence and cytotoxicity assays, and under physiologically relevant flow conditions in a microscope perfusion incubator system. Blocking studies were performed using monoclonal antibodies specific for beta2 integrins and CD54, and specific peptides which inhibit sFn binding to these receptors. RESULTS: Enhancement of monocyte/tumor cell adherence was observed when only one cell type was bound to sFn, but profound inhibition was observed when sFn was bound to both monocytes and tumor cells. This effect was also reflected in the pattern of monocyte cytotoxicity. Studies using monoclonal blocking antibodies and specific blocking peptides (which did not affect normal coagulation) showed that the predominant mechanism of fibrin inhibition is via its binding to alphaM beta2 on monocytes, and to CD54 on both leukocytes and tumor cells. CONCLUSION: sFn inhibits monocyte adherence and cytotoxicity of tumor cells by blocking alphaL beta2 and alphaM beta2 binding to tumor cell CD54. These results demonstrate that sFn is immunosuppressive and may be directly involved in the etiology of metastasis. Use of specific peptides also inhibited this effect without affecting coagulation, suggesting their possible use as novel therapeutic agents in cancer metastasis.