Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Selection criteria for internal medicine residency applicants and professionalism ratings during internship.

OBJECTIVE: To determine whether standardized admissions data in residents' Electronic Residency Application Service (ERAS) submissions were associated with multisource assessments of professionalism during internship. PARTICIPANTS AND METHODS: ERAS applications for all internal medicine interns (N=191) at Mayo Clinic entering training between July 1, 2005, and July 1, 2008, were reviewed by 6 raters. Extracted data included United States Medical Licensing Examination scores, medicine clerkship grades, class rank, Alpha Omega Alpha membership, advanced degrees, awards, volunteer activities, research experiences, first author publications, career choice, and red flags in performance evaluations. Medical school reputation was quantified using U.S. News & World Report rankings. Strength of comparative statements in recommendation letters (0 = no comparative statement, 1 = equal to peers, 2 = top 20%, 3 = top 10% or "best") were also recorded. Validated multisource professionalism scores (5-point scales) were obtained for each intern. Associations between application variables and professionalism scores were examined using linear regression. RESULTS: The mean ± SD (minimum-maximum) professionalism score was 4.09 ± 0.31 (2.13-4.56). In multivariate analysis, professionalism scores were positively associated with mean strength of comparative statements in recommendation letters (ß = 0.13; P = .002). No other associations between ERAS application variables and professionalism scores were found. CONCLUSION: Comparative statements in recommendation letters for internal medicine residency applicants were associated with professionalism scores during internship. Other variables traditionally examined when selecting residents were not associated with professionalism. These findings suggest that faculty physicians' direct observations, as reflected in letters of recommendation, are useful indicators of what constitutes a best student. Residency selection committees should scrutinize applicants' letters for strongly favorable comparative statements.

An MLL-SEPT9 fusion and t(11;17)(q23;q25) associated with de novo myelodysplastic syndrome.

Rearrangements of the MLL gene at chromosome 11q23 are uncommon in de novo myelodysplastic syndrome (MDS). Here, we describe molecular findings in a patient with multilineage dysplasia and t(11;17)(q23;q25) who responded to decitabine therapy. Fluorescent in situ hybridization (FISH) demonstrated rearrangement of MLL, while RT-PCR analysis and sequencing identified the transcript fusion partner as SEPT9, a member of the septin family of GTPases. MLL-SEPT9 fusion appears to be rare, having been described to date in only seven cases of AML and not, to our knowledge, in MDS. Analysis of MLL-septin family member fusion products such as the one seen here may provide further insights into the etiology of myeloid neoplasia, and MLL-SEPT9 fusion may be worth seeking in other cases of MLL rearrangements with a translocation partner on chromosome 17q.