A computer protocol to predict myocardial infarction in emergency department patients with chest pain

To achieve more appropriate triage to the coronary care unit of patients presenting with acute chest pain, we used clinical data on 1379 patients at two hospitals to construct a simple computer protocol to predict the presence of myocardial infarction. When we tested this protocol prospectively in 4770 patients at two university hospitals and four community hospitals, the computer-derived protocol had a significantly higher specificity (74 vs. 71 percent) in predicting the absence of infarction than physicians deciding whether to admit patients to the coronary care unit, and it had a similar sensitivity in detecting the presence of infarction (88.0 vs. 87.8 percent). Decisions based solely on the computer protocol would have reduced the admission of patients without infarction to the coronary care unit by 11.5 percent without adversely affecting the admission of patients in whom emergent complications developed that required intensive care. Although this protocol should not be used to override careful clinical judgment in individual cases, the computer protocol for the most part yields accurate estimates of the probability of myocardial infarction. Decisions about admission to the coronary care unit based on the protocol would have been as effective as those actually made by the unaided physicians who cared for the patients, and less costly. Whether physicians who are aided by the protocol perform better than unaided physicians cannot be determined without further study.     

Ruling out acute myocardial infarction. A prospective multicenter validation of a 12-hour strategy for patients at low risk

BACKGROUND. Although previous investigations have suggested that 24 hours is required to exclude acute myocardial infarction in patients who are admitted to a coronary care unit for the evaluation of acute chest pain, we hypothesized that a 12-hour period might be adequate for patients with a low probability of infarction at the time of admission. METHODS. Using a Bayesian model, we developed a strategy to identify candidates for a shorter period of observation from an analysis of a derivation set of 976 patients with acute chest pain who were admitted to three teaching and four community hospitals. In the derivation set, patients whose clinical characteristics in the emergency room predicted a low (less than or equal to 7 percent) probability of myocardial infarction had only a 0.4 percent risk of infarction if they had neither abnormal levels of cardiac enzymes nor recurrent ischemic pain during the first 12 hours of hospitalization. In an independent testing set of 2684 patients from the seven hospitals, 957 admitted patients (36 percent) were classified as candidates for this 12-hour period of observation according to a previously published multivariate algorithm. Few of these patients were actually transferred from a monitored setting at 12 hours. RESULTS. Of the 771 candidates for a 12-hour period of observation who did not have enzyme abnormalities or recurrent pain during the first 12 hours, 4 (0.5 percent) were subsequently found to have acute myocardial infarction, and only 3 (0.4 percent) died after primary cardiac arrests, all of which occurred three to five days after admission. Rates of other major cardiovascular complications were low in the patients who might have been transferred from the coronary care unit after 12 hours with this strategy. In patients with a higher initial risk of infarction, the standard strategy of 24-hour observation identified all but 11 of 739 acute myocardial infarctions (1 percent). CONCLUSIONS. Emergency room clinical data can be used to identify a large subgroup of patients for whom a 12-hour period of observation is normally sufficient to exclude acute myocardial infarction. Patient-specific evaluation and treatment can then proceed without the restrictions imposed by "rule-out" protocols for myocardial infarction.     

Outcomes in patients with myocardial infarction who are initially admitted to stepdown units: data from the Multicenter Chest Pain Study

PURPOSE: To assess whether the admission of patients with chest pain to a stepdown unit would jeopardize the outcome of those patients who ultimately "ruled in" for a myocardial infarction. PATIENTS AND METHODS: We compared the risk of an adverse outcome in initially uncomplicated, "rule-out myocardial infarction" patients who were admitted directly to a stepdown unit (n = 58) or to a coronary care unit (n = 409) at 6 hospitals and who then ultimately "ruled in" for a myocardial infarction. RESULTS: An adverse outcome (death, serious complication, or invasive intervention) occurred in 16 (28%) stepdown unit patients compared with 159 (39%) coronary care unit patients. Among patients eligible for initial care in either location, the risk of an adverse outcome after controlling for clinical characteristics was similar in the two groups using each of two different multivariate approaches. CONCLUSION: Although our study was not of sufficient size to exclude the possibility of a small benefit from initial triage to a coronary care unit, our data suggest that (1) admission of initially uncomplicated chest pain patients with a relatively low probability of acute myocardial infarction to a stepdown unit does not seriously jeopardize those who eventually "rule in" for myocardial infarction; and (2) larger observational or randomized studies, which could reduce the residual possibility of somewhat higher risk in the stepdown unit, would be ethical to perform.     

Genetic interaction between the non-homologous end-joining factors during B and T lymphocyte development: In vivo mouse models

Non-homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double-strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, PAXX, MRI) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.     

A Multiple Choice Testing Program Coupled with a Year-long Elective Experience is Associated with Improved Performance on the Internal Medicine In-Training Examination

Background  

The Internal Medicine In-Training Exam (IM-ITE) assesses the content knowledge of internal medicine trainees. Many programs use the IM-ITE to counsel residents, to create individual remediation plans, and to make fundamental programmatic and curricular modifications.     

Divergent effects of two sequence variants of GJB3 (G12D and R32W) on the function of connexin 31 in vitro

Recently, we identified several missense mutations of the connexin gene GJB3 encoding connexin 31 (Cx31) in erythrokeratodermia variabilis (EKV), an autosomal dominant skin disorder. These mutations include G12D, which replaces a conserved glycine residue in the amino-terminus of Cx31 and is associated with a severe EKV phenotype. In contrast, the biologic relevance of the GJB3 sequence variant R32W located in the first transmembrane domain of Cx31 is disputed. To examine the effects of these sequence variants on Cx31 biogenesis and gap junction activity we expressed wild type and mutant Cx31-Flag constructs in HeLa cells. Using immunostaining, all expression variants were detected in the cytoplasm and in a punctate pattern at the cell surface, indicating that G12D and R32W did not interfere with either protein synthesis or transport to the cell membrane. Similarly, oligomerization into hemichannels appeared not impaired when expressing either Cx31 mutant as assessed by size exclusion chromatography, immunoblotting and immunostaining. However, dye transfer experiments and monitoring of intracellular calcium levels in response to serum stimulation revealed that G12D-Cx31 did not form functional gap junction channels, probably due to incorrect assembly or altered properties of Cx31 channels. In contrast, intercellular coupling between cells expressing R32W-Cx31 was comparable to that of wtCx31, suggesting that R32W is a functionally inconsequential polymorphism of Cx31.     

An ambulatory medical education program for internal medicine residents

Teaching the fundamentals of ambulatory medicine has many well known difficulties. An education program with specific topics covered and modeled after continuing medical education programs for practicing physicians was instituted for residents in a university hospital clinic and was evaluated. The program was effective in improving the residents' knowledge, in enhancing their attitudes toward the clinic, and in improving their performance of influenza vaccinations. No adverse effects of the program were found. This approach, in which a curriculum is carefully defined and participation of the house staff is required, makes the ambulatory medical education process more accountable for what is taught.     

Myocardial rescue with autologous mitochondrial transplantation in a porcine model of ischemia/reperfusion

Objective

To demonstrate the clinical efficacy of autologous mitochondrial transplantation in preparation for translation to human application using an in vivo swine model.